Table 1.

The effects and mechanisms of CTSK in cancers.

Cancer Type	Research Samples	Effects	Mechanism	Refs.
Prostate
Prostate cancer	LNCaP cells; C4-2B cells; PC3 cells; Patient tissue; Patient serum	CTSK promotes invasion and metastasis of prostate cancer; CTSK promotes cytokine Release;	CTSK mediates bone matrix degradation; CTSK is involved in CCL2- and Cox-2-driven pathways;	[44]
Breast
Breast cancer	MCF-7 cells; MDA-MB-231 cells; Hs578T cells	CTSK is highly expressed in mammary fibroblasts; CTSK promotes breast cancer cells to metastasize to other sites	CTSK interacts with RANKL/RANK; CTSK degrades ECM and activates MMP-9 to promote breast cancer metastasis; CTSK promoter selectively overexpresses BCA3, which interacts with Rac1 and is associated with NF-κB signaling.	[21,54,127,128]
Breast cancer with bone metastasis	MDA-MB-231Hi cells	CTSK is strongly expressed after bone metastases in breast cancer; CTSK degrade extracellular matrix;	Both RANKL and TGF-β can induce the transcription factor NFATc1 to accumulate in the nucleus, and NFATc1 binds to the promoter and directly induces the expression of Src and CTSK; The high expression of IL-20 upregulates CTSK and MMP-9, and promotes bone metastasis of breast cancer	[66]
Bone
Giant cell tumor of bone	osteoclast-like giant cells; multinucleated giant cells	CTSK is abundantly expressed in the multinucleated giant cells and its activity, which was more than 100-fold higher than activities found in other tissues expressing CTSK	CTSK degrades collagen matrix; CTSK/V-ATPase system is primarily proteolytic factors leading to osteolysis of GCT of bone	[18]
Kidney
CRC	Xp11TRC cells; Renal cells	CTSK is positive; CTSK can be used as an immunodiagnostic marker	CTSK is a transcriptional target of Mitf and TFE3; TFE3 gene rearrangement and TFEB gene amplification lead to the invasion and migration of renal cell carcinoma, and the expression level of CTSK is higher; t (6;11) (p21; q12) translocation; TSC1/TSC2 mutation promotes renal cell carcinoma development; CTSK inhibitor significantly reduced mTOR phosphorylation at S2448 in Caki cells and inhibited renal cell carcinoma progression.	[76,77,78,119,122]
CCRCC	CCRCC cells	CTSK is positive	CTSK and mTOR expression is dysregulated	[81,82]
PRCC	PRCC cells	CTSK is positive	CTSK and mTOR expression is dysregulated	[28]
CRCC	CRCC cells	CTSK is positive	CTSK and mTOR expression is dysregulated	[28]
Sporadic RCC	RCC cells	CTSK is positive	CTSK and mTOR expression is dysregulated	[28,123]
Lung
NSCLC	SBC-5 cells; A549 cells; Patient tissues; Patient serum; Mice tissues	CTSK maintains airway structural integrity; CTSK strongly expressed;	CTSK binds to TGF-β1 and activates the pathway to promote tumor metastasis; CTSK promotes NSCLC invasion and metastasis by activating mTOR signaling pathway; mTOR/S6K/rS6; EGFR/Akt/mTOR pathway plays a role;	[129,130,131,132,133]
ADC	Patient tissues	CTSK is positive	TGF-β1 acts as a potent substrate for CTSK.	[133]
ADC	Patient tissues	CTSK is positive	CTSK activates mTOR signaling pathway mTOR/S6K/rS6 axis comes into play;	[134]
SqCC	Patient tissues	CTSK is positive	Increased expression of p-mTOR, so it associated with the mTOR pathway	[133,135]
LCC	Patient tissues	Not mentioned	Not mentioned
Others
Colorectal cancer	MC38 cells; SW480 cells; RKO cells; Mice serum	Serum CTSK levels were significantly elevated in mice with intestinal flora imbalance; CTSK contributes to the aggressive phenotype of CRC cells in vitro and in vivo; CTSK as a prognostic biomarker	APC, TP53, KRAS, SMAD4 and PIK3CA mutations promote the occurrence of colorectal cancer; CTSK can stimulate M2-TAMs to secrete cytokines such as IL-10 and IL-17, and then promote the invasion and metastasis of colorectal cancer cells through the NF-κB pathway; CTSK binds to TLR4 and stimulates M2 polarization in tumor-associated macrophages through mTOR pathway. TLR signaling leads to phosphorylation and activation of microphthalmia transcription factors through p38, acting on the CTSK promoter	[94,95,97,99]
Ovarian cancer	OCa cells; Patient serum	CTSK promotes the metastasis of ovarian cancer; The expression of CTSK in peritoneal metastatic ovarian cancer was significantly higher than that in primary ovarian cancer; CTSK is a useful marker for the diagnosis of primary OCs with specific enhancement in combination with CA25 and HE4	AGAP2-AS1 inhibits cell metastasis and proliferation by inhibiting epithelial-mesenchymal transition by downregulating CTSK; Downregulation of NDRG1 reduces the expression of pro-invasive genes CTSK, MMP-7 and TMPRSS4	[101,104,105,106]
Gastric cancer	AGS cells; Gastric epithelial cells and macrophages; Gastric parietal cells	high expression of CTSK in gastric cancer cells; CTSK promotes the metastasis of gastric cancer;	CTSK promotes gastric cancer metastasis as a downstream factor of cytoskeletal protein Coronin 3; CTSK rapidly degrades ECM; CTSK cleaves and activates MMP-9 to promote gastric cancer cell proliferation and migration;	[108]
Melanoma	Melanoma cells	CTSK is significantly expressed in skin and fibroblasts; CTSK is positive in most primary melanomas and all cutaneous melanoma metastases;	Through the secretion of MMP and CTSK through the lymph and blood, the internal collagen is cut off, which promotes the penetration of melanoma cells into the dermis and achieves distant metastasis; CTSK may mediate the degradation of matrix proteins after phagocytosis and promote the invasion and metastasis of melanocytes	[113,114,115]