Skip to main content
NCBI home page
Discover Oncology logoLink to Discover Oncology
. 2025 Sep 29;16:1755. doi: 10.1007/s12672-025-03584-y

ATG7-induced autophagy inhibits ferroptosis and promotes the progression of colorectal adenocarcinoma

Minyuan Chen 1,✉, Ziqi Meng 1, Limei Zhu 1, Jieyu Liu 1
PMCID: PMC12480220  PMID: 41021143

Abstract

Purpose

To investigate the role of ATG7-induced autophagy in regulating ferroptosis and promoting the progression of colorectal adenocarcinoma (COAD).

Method

The UALCAN database was used to predict the expression of ATG7 and its prognosis significance in patients with COAD. The expression levels of ATG7 in HCT8 and SW620 cells were analyzed using qPCR and Western blot analyses. Functional assays, including the CCK-8 and Transwell assays, were conducted to assess the effects of ATG7 overexpression on cell proliferation and migration. Protein-protein interaction analyses were performed using GeneMANIA and STRING to explore the relationships between ATG7, autophagy-related proteins, and markers of ferroptosis. Autophagy was inhibited using 3-MA, while ferroptosis was induced with erastin in ATG7-overexpressing COAD cells to elucidate their interactions.

Results

Overexpression of ATG7 in COAD cells enhanced cell proliferation and migration, while inhibiting ferroptosis by decreasing levels of Fe2+ and MDA and increasing level of GSH. Mechanistically, ATG7-induced autophagy downregulated ACSL4 and upregulated GPX4, which are key regulators of ferroptosis. Pretreatment with 3-MA reversed these effects, thereby confirming the role of autophagy in modulating ferroptosis in COAD cells that overexpress ATG7.

Conclusion

These findings suggest that targeting ATG7-mediated autophagy may serve as a therapeutic strategy for COAD by increasing susceptibility to ferroptosis-induced cell death.

Keywords: ATG7, Autophagy, Ferroptosis, Colorectal cancer, Proliferation, Migration

Introduction

Colorectal adenocarcinoma (COAD) presents a significant global health challenge, contributing substantially to cancer-related morbidity and mortality worldwide [1–3]. It is one of the most common malignancies, with a concerning increase in incidence rates reported across various demographic groups [4, 5]. Epidemiological data clearly demonstrate its severe impact, with COAD ranking among the leading causes of cancer-related deaths globally [6–8]. This highlights an urgent need for innovative therapeutic strategies to address its rising prevalence and enhance patient outcomes.

Autophagy-related protein ATG7 has garnered significant attention for its crucial role in cellular processes, particularly in regulating ferroptosis-a form of iron-dependent cell death implicated in cancer progression [9–11]. ATG7 has been shown to play a role in the regulation of ferroptosis [12, 13]. GATA6 inhibits neuronal ferroptosis in cerebral ischemia-reperfusion injury by regulating the miR-193b/ATG7 axis [14]. Recent studies indicate that inducing ferroptosis can help overcome chemotherapy resistance in cancer cells [15, 16]. Zeng et al. discovered that inhibiting ACSL4-mediated ferroptosis confers oxaliplatin resistance to COAD cells [15]. Ferroptosis is increasingly recognized as a potential therapeutic target in COAD due to its unique mechanisms and associations with tumor development and treatment resistance [17–19]. Understanding the interplay between ATG7 and ferroptosis pathways could provide novel insights into the pathogenesis of COAD and inform therapeutic strategies [20–22].

This study aims to elucidate the role of ATG7-induced autophagy in modulating ferroptosis and its impact on the progression of COAD. By investigating how ATG7 influences ferroptosis and associated cellular responses, this research seeks to address fundamental questions regarding COAD biology and potential therapeutic interventions. Ultimately, unraveling these mechanisms holds promise for developing targeted therapies that enhance susceptibility to ferroptosis-induced cell death in COAD, thereby improving clinical outcomes and patient survival.

Method and material

Bioanalysis

UALCAN database was used to analyze the expression levels of ATG7 in COAD tissues compared to normal tissues. The Kaplan-Meier plotter was employed to assess the impact of ATG7 on survival in COAD. In addition, GeneMANIA and STRING were used to conduct protein interaction network analysis.

Cell line

The normal human intestinal epithelial cells, HIEC-6, along with the COAD cell lines HCT8 and SW620, and the HEK-293T cell line, are all sourced from ATCC (Manassas, VA). These cell lines were cultured in DMEM or RPMI-1640, supplemented with 10% fetal bovine serum (FBS), at 37 °C in a 5% CO2 atmosphere.

Plasmids and stable cell constructions

We procured PCDH vectors that overexpress ATG7 and a negative control (PCDH-GFP) from Nangjing Hongde Biotech (Nangjing, China). Lentiviruses were generated in 293T cells using the pMDG and delta 8.9 as the lentivirus backbone. Lentivirus supernatants were harvested 24 and 48 h post-transfection and used to infect HCT8 and SW620 cells. Positive cells were selected 48 h after infection using 2 µg/mL puromycin (Millipore, USA).

Quantitative real-time PCR (qRT-PCR)

RNA extraction from specified cells was performed using TRIzol reagent (Takara, China), following the manufacturer’s instructions. Reverse transcription of 2 µg of total RNA was conducted using HiScript Reverse Transcriptase (Vazyme, China). For qRT-PCR assays, an ABI-Q5 real-time RT-PCR system and SYBR Green Real-time PCR Master Mix (Vazyme, China) were utilized. GAPDH was used as a control.

Western blotting

Typically, 5 × 105 cells per plate were seeded into a 6-cm dish and allowed to adhere for 24 h. Subsequently, cell lysis was performed using either 1% SDS or the specified lysis buffer, followed by boiling and SDS-PAGE electrophoresis. The separated proteins were then transferred onto a nitrocellulose membrane. After blocking with 5% skim milk for one hour at room temperature, the membranes were incubated overnight at 4 °C with primary antibodies, including ATG7 (CST), LC3II (CST), Beclin 1 (CST), p62 (CST), ACSL4 (CST), GPX4 (CST), and GAPDH (Proteintech). The following day, the membranes were washed with PBST (0.05% Tween-20) and incubated with either anti-mouse or anti-rabbit IgG-HRP.

CCK8 assay

COAD cells were seeded into 96-well plates at a density of 1 × 105 cells per well and cultured. Cells were collected at 0, 12, 24, 48, and 72 h. After removing the culture medium, CCK-8 reagent (diluted at 1:100) was added to each well of the 96-well plate. The plate was then incubated at 37 °C for 45 min. Absorbance values of each sample were measured at a wavelength of 450 nm using a spectrophotometer to calculate the results.

Transwell assay

COAD cells (1 × 104) were seeded into the upper chamber of a pre-prepared 0.8 μm Transwell insert. The Transwell insert was then placed into a 24-well plate containing either culture medium or drug-containing serum in the lower chamber. After 24 h of incubation, the Transwell insert was removed from the 24-well plate, and the medium was carefully discarded. The cells were gently wiped off using a cotton swab. Subsequently, the cells in the upper chamber was fixed by placing the insert in a 24-well plate containing 4% paraformaldehyde for 15 min. The insert was washed three times with PBS, then immersed in 1% crystal violet solution for 30 min. After removing the insert, it was wash three times with PBS, air-dried it at room temperature, and observed under a light microscope for imaging and counting. Statistical analysis was performed on the counted cells.

Fe2+ detection

The iron assay kit (Abcam, ab83366) was used to analyze Fe2+ levels. Add 5 µL of Iron Reducer to each well containing the standard. For the iron (II) assay, add 5 µL of Assay Buffer to each sample. Thoroughly mix and incubate the standards and samples at 37 °C for 30 min. Subsequently, add 100 µL of Iron Probe to each well containing either Iron Standard I, Iron Standard II, or the test samples. Mix gently and incubate at 37 °C for 60 min, protected from light. Measure the absorbance immediately using a colorimetric microplate reader at a wavelength of 593 nm.

GSH content assay

The GSH Assay Kit (Beyotime) was employed to determine the GSH content. Using a 96-well plate, samples or standard solutions were sequentially added and mixed. After adding 150 µL of the total glutathione detection working solution, the mixture was thoroughly mixed and incubated at 25 °C (room temperature) for 5 min. Subsequently, 50 µL of a 0.5 mg/mL NADPH solution was added and mixed. The absorbance at 412 nm was then measured using a microplate reader, with readings taken every 5 min or continuously over a total period of 25 min.

MDA detection

The Lipid Peroxidation (MDA) Assay Kit (Beyotime) was used to measure the MDA content. First, an appropriate amount of TBA was weighed and dissolved to prepare a 0.37% TBA stock solution. The MDA detection working solution was then prepared. For blank controls, 0.1 mL of homogenate, lysate, or PBS was added to centrifuge tubes or suitable containers. To create a standard curve, 0.1 mL of different concentrations of the standard solution was added. For sample analysis, 0.1 mL of the sample was included. Subsequently, 0.2 mL of the MDA detection working solution was added. After thorough mixing, the mixture was heated at 100 °C or in a boiling water bath for 15 min. The water bath was then allowed to cool to room temperature, followed by centrifugation at 1000 g for 10 min at room temperature. Two hundred microliters of the supernatant was transferred to a 96-well plate, and the absorbance was measured at 532 nm.

Statistical analysis

The results are presented as means ± standard deviation (SD). Group comparisons were evaluated using Student’s t-test, with statistical significance established at P < 0.05. All outcomes were confirmed through a minimum of three independent experiments.

Results

ATG7 promotes the proliferation and migration of COD cells

Initially, we analyzed the expression of ATG7 in clinical patients with COAD and its association with patient prognosis using the UALCAN database and Kaplan-Meier plotter. The results indicated that ATG7 expression level was significantly increased in patients with COAD, and high expression levels of ATG7 in COAD patients significantly shortened their clinical survival (Fig. 1a, b). Subsequently, we validated this finding in different colon cancer cell lines (HCT8 and SW620). QPCR and Western blot analyses demonstrated a significant increase in ATG7 expression in HCT8 and SW620 cells compared to the HIEC-6 group (Fig. 1c, d). To investigate whether ATG7 is involved in regulating autophagy in COAD, we separately transfected PCDH-ATG7 into HCT8 and SW620 cells. The results showed a significant increase in ATG7 expression in the ATG7 group compared to the Vector group(Fig. 1e, f). Subsequently, the CCK-8 assays revealed that the overexpression of ATG7 in COAD cells significantly promoted the proliferation of HCT8 and SW620 cells (Fig. 1i). Furthermore, Transwell assays demonstrated that ATG7 overexpression also enhanced the migration of HCT8 and SW620 cells compared to the Vector group (Fig. 1j). Additionally, we examined the expression of key autophagy-regulating proteins, including LC3II, Beclin 1, and p62 in HCT8 and SW620 cells overexpressing ATG7. The results indicated a significant upregulation of LC3II, Beclin 1, and p62 expression in the ATG7 groups (Fig. 1g, h), suggesting that ATG7 plays a pro-oncogenic role in COAD by regulating cell autophagy.

Fig. 1.

Fig. 1

Open in a new tab

Autophagy-related ATG7 promotes the COAD proliferation and migration. a Expression and prognostic prediction of ATG7 in b tumor patients. c, d Detection of ATG7 expression in NIEC-8, HCT8, and SW620 cells. e, f Detection of overexpression efficiency of ATG7 in HCT8 and SW620 cells. g, h Detection of autophagy related proteins LC3II, Beclin1, and p62 expression after overexpression of ATG7 in HCT8 and SW620 cells. i The CCK8 experiment was used to detect the effect of overexpression of ATG7 on the proliferation of HCT8 and SW620. j The Transwell experiment was used to detect the effect of overexpression of ATG7 on the invasion of HCT8 and SW620. n = 3,**P<0.01, ***P<0.001

ATG7 is involved in ferroptosis in COAD

Iron-dependent cell death, known as ferroptosis, is a significant form of cellular demise. Studies have implicated ATG7 in regulating processes related to ferroptosis [23–25]. However, there are currently no reports demonstrating the involvement of ATG7 in regulating ferroptosis processes in COAD. Therefore, in HCT8 and SW620 cells overexpressing ATG7 (ATG7 group), we assessed the expression of ferroptosis-related metabolites, including Fe2+, MDA, and GSH. The results indicated a significant decrease in Fe2+ and MDA levels, along with a notable increase in GSH levels in the ATG7 group(Fig. 2a-f). Additionally, ferroptosis-related proteins such as ACSL4 and GPX4 exhibited a decrease and increase, respectively (Fig. 2g, h). These findings suggest that in COAD, ATG7 suppresses cellular ferroptosis processes in COAD.

Fig. 2.

Fig. 2

Open in a new tab

ATG7 involves in the COAD ferroptosis. a, b, c Detection of Fe2+, MDA, and GSH content after overexpression of ATG7 in HCT8 cells. d, e, f The content of Fe2+, MDA, and GSH in SW620 cellsafter overexpression of ATG7. g, h The ACSL4 and GPX4 protein expression in HCT8 and SW620 cells overexpressing ATG7.n = 3,**P<0.01, ***P<0.001

ATG7 regulates ferroptosis in COAD by mediating cell autophagy

ATG7 is an E1-like ubiquitin-activating enzyme that plays a crucial role in autophagy, while Beclin1 is a well established regulator of this process [26–28]. Research has indicated that autophagy is involved in the regulation of the ferroptosis pathway [29, 30]. To investigate how ATG7 influences ferroptosis in COAD cells, protein-protein interaction (PPI) analyses were conducted using GeneMANIA and STRING. The results revealed that Beclin1 acts as a central hub, connecting ATG7 with ferroptosis-related proteins such as PTGS2, NOX1, FTH1, GPX4, and ACSL4 (Fig. 3a, b). This finding suggests that ATG7-mediated cellular autophagy may play a regulatory role in the process of ferroptosis in COAD.

Fig. 3.

Fig. 3

Open in a new tab

ATG7 controls the COAD ferroptosis by mediating the cell autophagy. a, b Analysis of the interaction between bATG7 and ferroptosis related proteins. c, d Detection of autophagy related protein expression after 3-MA treatment. e, f Analysis of Fe2+, MDA, and GSH content after 3-MA treatment. g, h Detection of ferroptosis related proteins ACSL4 and GPX4 expression after 3-MA treatment。n = 3,*P<0.05 vs. Control, #P<0.05 vs. Vector + 3-MA

Subsequently, COAD cells were pretreated with 2 µM of the autophagy inhibitor 3-MA for 2 h. The results demonstrated that 3-MA effectively reduced the expression of autophagy-related proteins LC3II, Beclin1, and p62 in the ATG7 group of HCT8 and SW620 cells (Fig. 3c, d). Furthermore, upon further examination of ferroptosis-related markers in 3-MA-treated COAD cells, it was observed that 3-MA significantly decreased levels of Fe2+ and MDA while increasing GSH levels in ATG7 group of HCT8 and SW620 cells (Fig. 3e, f). Additionally, 3-MA reduced ACSL4 protein expression and promoted GPX4 protein expression in HCT8 and SW620 cells overexpressing ATG7 (Fig. 3g, h). These findings indicate that ATG7-mediated autophagy in COAD suppresses ferroptosis processes.

Erastin migrates the inhibitory effect of ATG7 on the ferroptosis of OCAD cells

To further confirm that ATG7-mediated autophagy suppresses ferroptosis processes in COAD, we treated COAD cells overexpressing ATG7 with the ferroptosis agonist erastin. We assessed cell viability of COAD cells after treatment with different concentrations of erastin for 24, 48, and 72 h. The data presented in Fig. 4a indicate that erastin reduced the viability of COAD cells as the concentration of erastin increased. The 24-hour IC50 value for COAD cells treated with erastin were 24.80 µM for HCT8 cells and 21.94 µM for SW620 cells. This suggests that, compared to the Control group, erastin pretreatment resulted in elevated levels of in Fe2+ and MDA, while decreasing GSH level (Fig. 4b, c). In cells pretreated with erastin, overexpression of ATG7 significantly reduced the levels of Fe2+ and MDA, while increasing GSH level. However, the presence of 3-MA negated the effects of ATG7 on Fe2+, MDA, and GSH. Furthermore, we observed that erastin increased both mRNA and protein expression of ACSL4 while decreasing GPX4 expression in COAD cells (Fig. 4d, e). Compared to the Vector + erastin group, the ATG7 + erastin group exhibited elevated level of ACSL4 and reduced level of GPX4. However, 3-MA negated the increase in ACSL4 and the decrease in GPX4 in COAD cells (Fig. 4d, e). Additionally, we assessed the proliferation and migration capabilities of these cells following erastin treatment. Compared to the Control group, the proliferation and migration of COAD cells were markedly reduced in the Vector + erastin group. In contrast, the ATG7 + erastin group demonstrated enhanced proliferation and migration compared to the Vector + erastin group (Fig. 4f, g). However, 3-MA negated the increase in proliferation and migration of COAD cells. These findings confirm the regulatory role of ATG7 in autophagy-dependent ferroptosis in COAD cells.

Fig. 4.

Fig. 4

Open in a new tab

Inhibiting autophagy can alleviate the inhibition of overexpressed ATG7-COAD cell ferroptosis treated with erastin. a The cell viability of CRC cells after treatment with erastin. b, c After treatment with erastin, the levels of Fe2+, MDA, and GSH in the cells were detected. d, e Analysis of ACSL4 and GPX4 protein expression in cells treated with erastin. f Analysis of HCT8 and SW620 cell proliferation after treatment with erastin. Analysis of HCT8 and SW620 cell invasion after treatment with erastin. n = 3,*P<0.05 vs. Control, #P<0.05 vs.Vector + erastin, &P<0.05 vs. ATG7 + srastin

Discussion

In this study, we investigated the role of ATG7 in COAD, focusing on its implications for cellular processes related to both autophagy and ferroptosis. Our findings reveal that ATG7 overexpression significantly promotes the proliferation and migration of COAD cells, underscoring its potential as a key regulator in cancer progression. Furthermore, we observed that ATG7-mediated autophagy enhances cellular resistance to ferroptotic cell death, indicating a complex interplay between these pathways in the pathophysiology of COAD.

Our results corroborate and extend the existing literature on ATG7 and its functions in cancer biology [31]. Consistent with previous reports, we found that elevated ATG7 expression correlates with adverse clinical outcomes in COAD patients, emphasizing its prognostic significance [32–34]. The observed increase in ATG7 expression in COAD cell lines (HCT8 and SW620) aligns with studies that implicate ATG7 in promoting tumor cell survival and aggressiveness through the modulation of autophagy-related processes. This supports the notion that ATG7 plays a critical player in driving oncogenic behaviors by enhancing cellular proliferation and migration capacities [35–37].

Furthermore, our investigation into ATG7’s role in ferroptosis represents a significant contribution to the field. While previous research has examined ATG7’s function in autophagy, its impact on ferroptosis pathways in COAD cells has not been thoroughly explored. PPI network analysis revealed that ATG7 mediated ferroptosis through Beclin 1. Overexpression of ATG7 significantly reduced the expression of ferroptosis promoter ACSL4 while enhancing the expression of the ferroptosis inhibitor GPX4. However, pretreatment with the autophagy inhibitor 3-MA led to a downregulation of GPX4 and an upregulation of ACSL4. These findings suggest that ATG7 facilitates the malignant progression of COAD by inhibiting ferroptosis, thereby promoting the proliferation and migration of COAD cells.

Our study offers crucial insights into the complex interplay between ATG7-mediated autophagy and ferroptosis in the pathogenesis of COAD. The identified regulatory roles of ATG7 indicate potential therapeutic strategies that target these pathways to reduce tumor progression and improve treatment efficacy. Approaches aimed at modulating ATG7 activity or its downstream effectors could provide innovative therapeutic options for COAD treatment, especially when combined with existing therapies that target autophagy or ferroptosis.

Conclusion

In summary, our study elucidates the critical role of ATG7 in COAD, highlighting its dual involvement in promoting cancer cell proliferation and migration while also suppressing ferroptosis processes through autophagy mediation. Elevated ATG7 expression in COAD correlates with poor clinical outcomes and increases cellular resistance to iron-dependent cell death, underscoring its significance in tumor progression. These findings position ATG7 as a potential therapeutic target for developing novel treatment strategies aimed at improving patient outcomes in COAD.

Acknowledgements

Not applicable.

Author contributions

Conception and design: Minyuan Chen; Provision of study materials: All authors; Collection and assembly of data: Ziqi Meng, Limei Zhu; Data analysis and interpretation: Ziqi Meng, Jieyu Liu; Manuscript writing: All authors; Final approval of manuscript: All authors.

Funding

The study was supported by Key Discipline Construction Project of Traditional Chinese Medicine in Zhejiang Province for 2024 (2024-XK-52).

Data availability

The data involved in this study include: relative expression data of ATG7, LC3II, Beclin1, p62, ACSL4, and GPX4 in COAD cell lines detected by qPCR and western blot; cell behavioral data related to proliferation and migration abilities detected by CCK-8 and Transwell assays; cell ferroptosis-relative data related to levels of Fe2+, GSH, and MDA in COAD cells lines detected by corresponding assay kits; and relative expfression data of ATG7 in 286 COAD tissues and 41 normal tissues analyzed based on TCGA database in UALCAN (https://ualcan.path.uab.edu/cgi-bin/TCGAExResultNew2.pl? genenam=ATG7&ctype=COAD); overall survival of ATG7 in COAD analyzed in Kaplan-Meier Plotter (Affy ID: 222709\_at). All results derived from the aforementioned data have been fully presented in the manuscript. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable. (This study was conducted in cells and did not involve human patients)

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Thanikachalam K, Khan G. Colorectal cancer and nutrition. Nutrients. 2019;11(1):164. [DOI] [PMC free article] [PubMed]
  • 2.Baidoun F, et al. Colorectal cancer epidemiology: recent trends and impact on outcomes. Curr Drug Targets. 2021;22(9):998–1009. [DOI] [PubMed] [Google Scholar]
  • 3.Haraldsdottir S, et al. Colorectal cancer—review. Laeknabladid. 2014;100(2):75–82. [DOI] [PubMed] [Google Scholar]
  • 4.Nfonsam V, et al. Early-Onset colorectal cancer. Surg Oncol Clin N Am. 2022;31(2):143–55. [DOI] [PubMed] [Google Scholar]
  • 5.Yan H, Talty R, Johnson CH. Targeting ferroptosis to treat colorectal cancer. Trends Cell Biol. 2023;33(3):185–8. [DOI] [PubMed] [Google Scholar]
  • 6.Zielińska A, et al. Management of pain in colorectal cancer patients. Crit Rev Oncol Hematol. 2021;157:103122. [DOI] [PubMed] [Google Scholar]
  • 7.Siegel RL, et al. Colorectal cancer in the young: epidemiology, prevention, management. Am Soc Clin Oncol Educ Book. 2020;40:1–14. [DOI] [PubMed] [Google Scholar]
  • 8.Hollis RH, Chu DI. Healthcare disparities and colorectal cancer. Surg Oncol Clin N Am. 2022;31(2):157–69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Collier JJ, et al. Emerging roles of ATG7 in human health and disease. EMBO Mol Med. 2021;13(12):e14824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Zheng W, et al. ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell Commun Signal. 2019;17(1):42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Long JS, et al. ATG7 is a haploinsufficient repressor of tumor progression and promoter of metastasis. Proc Natl Acad Sci U S A. 2022;119(28):e2113465119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Han S, et al. USP13 regulates ferroptosis in chicken follicle granulosa cells by deubiquitinating ATG7. Poult Sci. 2024;103(11):104209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Jiang JJ, et al. [Effects of ATG5 and ATG7 knockout on ferroptosis sensitivity of RPMI-8226 cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024;32(5):1444–9. [DOI] [PubMed] [Google Scholar]
  • 14.Fan W, et al. GATA6 inhibits neuronal autophagy and ferroptosis in cerebral ischemia-reperfusion injury through a miR-193b/ATG7 axis-dependent mechanism. Neurochem Res. 2023;48(8):2552–67. [DOI] [PubMed] [Google Scholar]
  • 15.Wang Y, et al. Overcoming cancer chemotherapy resistance by the induction of ferroptosis. Drug Resist Updat. 2023;66:100916. [DOI] [PubMed] [Google Scholar]
  • 16.Zhang C, et al. Ferroptosis in cancer therapy: a novel approach to reversing drug resistance. Mol Cancer. 2022;21(1):47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Hou W, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12(8):1425–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Liu M, et al. Ferroptosis inducer Erastin sensitizes NSCLC cells to Celastrol through activation of the ROS-mitochondrial fission-mitophagy axis. Mol Oncol. 2021;15(8):2084–105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Wang ZX, et al. Quercetin induces p53-independent cancer cell death through lysosome activation by the transcription factor EB and reactive oxygen Species-dependent ferroptosis. Br J Pharmacol. 2021;178(5):1133–48. [DOI] [PubMed] [Google Scholar]
  • 20.Kim NY, et al. Cannabidiol induces ERK activation and ROS production to promote autophagy and ferroptosis in glioblastoma cells. Chem Biol Interact. 2024;394:110995. [DOI] [PubMed] [Google Scholar]
  • 21.Zhao L, et al. β-Lapachone induces ferroptosis of colorectal cancer cells via NCOA4-mediated ferritinophagy by activating JNK pathway. Chem Biol Interact. 2024;389:110866. [DOI] [PubMed] [Google Scholar]
  • 22.Sun W, et al. Autophagy-Dependent Ferroptosis-Related signature is closely associated with the prognosis and tumor immune escape of patients with glioma. Int J Gen Med. 2022;15:253–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Lin C, et al. Ferroptosis-based molecular prognostic model for adrenocortical carcinoma based on least absolute shrinkage and selection operator regression. J Clin Lab Anal. 2022;36(6):e24465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22(4):266–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Zeng F, et al. Ferroptosis detection: from approaches to applications. Angew Chem Int Ed Engl. 2023;62(35):e202300379. [DOI] [PubMed] [Google Scholar]
  • 26.Chen J, et al. Role of ATG7-dependent non-autophagic pathway in angiogenesis. Front Pharmacol. 2023;14:1266311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Yao H, et al. Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy. 2023;19(5):1491–511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Xiong J. Atg7 in development and disease: panacea or pandora’s box?? Protein Cell. 2015;6(10):722–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Wu J, et al. Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction. Front Cardiovasc Med. 2022;9:993592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Chen H et al. Ferroptosis and its multifaceted role in cancer: mechanisms and therapeutic approach. Antioxid (Basel). 2022;11(8):1504. [DOI] [PMC free article] [PubMed]
  • 31.Wang X, et al. m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy. 2020;16(7):1221–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Liu H et al. Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier. J Cell Biol. 2023;222(5):e202103098. [DOI] [PMC free article] [PubMed]
  • 33.Chen X, et al. Autophagy gene Atg7 regulates the development of radiation-induced skin injury and fibrosis of skin. Skin Res Technol. 2023;29(6):e13337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Arensman MD, et al. Anti-tumor immunity influences cancer cell reliance upon ATG7. Oncoimmunology. 2020;9(1):1800162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Koh M, et al. ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells. Autophagy. 2024;20(3):659–74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Shafi S, et al. Novel ATG7::RAF1 gene fusion in malignant glomus tumor. Genes Chromosomes Cancer. 2024;63(1):e23202. [DOI] [PubMed] [Google Scholar]
  • 37.Wu Z, et al. CDK12 Inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer. Pharmacol Res. 2024;201:107097. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data involved in this study include: relative expression data of ATG7, LC3II, Beclin1, p62, ACSL4, and GPX4 in COAD cell lines detected by qPCR and western blot; cell behavioral data related to proliferation and migration abilities detected by CCK-8 and Transwell assays; cell ferroptosis-relative data related to levels of Fe2+, GSH, and MDA in COAD cells lines detected by corresponding assay kits; and relative expfression data of ATG7 in 286 COAD tissues and 41 normal tissues analyzed based on TCGA database in UALCAN (https://ualcan.path.uab.edu/cgi-bin/TCGAExResultNew2.pl? genenam=ATG7&ctype=COAD); overall survival of ATG7 in COAD analyzed in Kaplan-Meier Plotter (Affy ID: 222709\_at). All results derived from the aforementioned data have been fully presented in the manuscript. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Articles from Discover Oncology are provided here courtesy of Springer

RESOURCES