TABLE 1.
Tumor suppressor versus promoter roles for PINK1 in various cancer types
| Cancer type | Samples | Potential mechanism | Function in tumorigenesis | Reference |
|---|---|---|---|---|
| Breast and liver cancer | HepG2, MCF‐7 | Inhibition of PINK1/Parkin‐dependent mitophagy sensitizes multidrug‐resistant cancer cells to B5G1 | PINK1/Parkin‐mediated mitophagy | 26 |
| Pancreatic cancer | PANC‐1, MIA PaCa2, TKF‐1, HepG2, HCT‐116, LO2, HK‐2 | PINK1/Parkin‐mediated mitophagy regulation by ROS alleviates rocaglamide A‐induced apoptosis | PINK1/Parkin‐mediated mitophagy | 33 |
| Hepatocellular carcinoma | HepG2 | Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and the PINK1/Parkin pathway | PINK1/Parkin‐mediated mitophagy | 27 |
| Breast cancer | MDA‐MB‐231 (HTB‐26) and MCF‐7 | Polyphyllin I induces mitophagic and apoptotic cell death by stabilization of full‐length PINK1 at the mitochondrial surface | PINK1/Parkin‐mediated mitophagy | 28 |
| Brain cancer | U87MG and T98G cells | SIRT1 activator Comp 5 induces mitophagy by the SIRT1–PINK1–Parkin pathway | PINK1/Parkin‐mediated mitophagy | 65 |
| Multiple cancers | PC‐3 and MDA‐MB‐231 | Chalocomoracin upregulates PINK1 mitophagy signaling, the novel pathway is triggered by ROS production | PINK1/Parkin‐mediated mitophagy | 66 |
| Tongue squamous cell carcinoma | 27 cell lines | ZnO nanoparticles increase ROS and decrease the mitochondrial membrane potential, activating PINK1/Parkin‐mediated mitophagy | PINK1/Parkin‐mediated mitophagy | 34 |
| Neuroblastoma cells | SH‐SY5Y | Mn induces PINK1/Parkin‐mediated mitophagy, exerting a neuroprotective effect against Mn‐induced dopaminergic neuronal cells apoptosis | PINK1/Parkin‐mediated mitophagy | 30 |
| Neuroblastoma cells | SH‐SY5Y | Chlorpyrifos treatment results in PINK1 stabilization on the outer mitochondrial membrane and subsequently increases Parkin recruitment from the cytosol to the abnormal mitochondria | PINK1/Parkin‐mediated mitophagy | 35 |
| Multiple cancers | MCF‐7, HeLa | Mitophagy induced by mROSA can initiate the sensitization of cancer cells to ionizing radiation through the Pink1/PARK2 pathway | PINK1/Parkin‐mediated mitophagy | 36 |
| Osteosarcoma | Saos‐2 and MG‐63 | Parthenolide (molecule interferes with NF‐Κb signaling) increases the autophagy and mitophagy, as characterized by increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy | PINK1/Parkin‐mediated mitophagy | 67 |
| Bladder cancer | EJ cell, nude mice, and patient serum sample | Antimony has its carcinogenic effect by inhibiting mitophagy dependent on the PINK1/Parkin pathway | PINK1/Parkin‐mediated mitophagy | 31 |
| Multiple cancers | MEF, HCT116, SH‐SY5Y, HEK293 | P53‐mediated negative regulation of autophagy is PINK1‐dependent, nuclear p53 controls PINK1 by repressing its promoter activity, and protein and mRNA levels | p53‐PINK1‐mitophagy | 41 |
| Hepatic cancer stem cells | Cell lines, transgenic mice, and patient samples | PINK1 binds to p53 on mitochondria and phosphorylates p53 at serine‐392, PINK1‐activated p53 is localized to the nucleus when mitophagy is impaired | p53‐PINK1‐mitophagy | 68 |
| Breast and lung cancer | Cell lines, transgenic mice, and patient samples | ARIH1 controls mitophagy of damaged mitochondrial in a PINK1‐dependent manner, protects cancer cells from chemotherapy‐induced death | PINK1/ARIH1‐mediated mitophagy | 29 |
| Colorectal cancer | 20 pairs of tumor samples | PINK1 is silenced in Colorectal cancer (CRC) adenocarcinoma in comparison to control | Tumor suppressor | 69 |
| Colorectal cancer | MC38, PINK1 knockout mice | PINK1 suppresses colon tumor growth by metabolic reprogramming via p53 activation and reducing acetyl‐CoA production | Tumor suppressor | 46 |
| Hepatocellular carcinoma | PLC/PRF/5, HepG2, and Hep3B |
Underexpression of PINK1 is detected in human HCC and associated with poor clinical outcomes Knockdown of PINK1 reduces mitochondrial mass and increases HCC growth (hypoxia/HIF/HEY1/PINK1/mitophagy) |
Tumor suppressor | 48 |
| Pancreatic cancer | Cell lines and transgenic mice | PINK1 suppresses pancreatic tumorigenesis through control of mitochondrial iron‐mediated immunometabolism | Tumor suppressor | 6 |
| Glioblastoma | Fetal human astrocytes, U87 and T98G cell lines, NOD‐SCID mice | PINK1 negatively regulates the Warburg effect and the growth of glioblastoma cells | Tumor suppressor | 5 |
| Lung cancer | Cell lines, BALB/c nu/nu mice | PINK1‐CTD suppresses Epidermal growth factor receptor (EGFR) dimerization, activation and EGFR signaling, impedes EGFR‐driven tumorigenesis | Tumor suppressor | 47 |
| Lung cancer | H1299 and SPC‐A‐1, nude mice | PINK1 suppression enhances apoptosis rate, the expression of Bax, cleaved caspase 3, and poly ADP ribose polymerase (PARP), decreased migration and invasion abilities | Oncogene | 70 |
| Lung cancer | 256 patients with nonsmall‐cell lung cancer | High PINK1 expression is correlated with poor response to hemotherapy and is an independent prognostic factor for adenocarcinoma, but not for squamous cell carcinoma | Oncogene | 7 |
| Multiple cancers | PINK1 knockout mice and derived MEF cell lines, MEFs, MCF‐7, and HeLa | PINK1 regulates cell cycle progression, reduced cancer associated phenotypes, including cell proliferation, colony formation, and invasiveness | Oncogene | 8 |
| Esophageal squamous cell carcinoma | 217 ESCC patients | High expression of PINK1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy | Oncogene | 9 |
| Lung cancer | 87 paired nonsmall‐cell lung cancer tissues, A549 and H1975 | PINK1 overexpression promotes cell migration and proliferation via regulation of autophagy and predicts a poor prognosis in lung cancer cases | Oncogene | 42 |
| Breast cancer | MDA‐MB‐231, transgenic mice | PINK1 drives production of Mitochondrial DNA (mtDNA)‐containing extracellular vesicles to promote invasiveness by activating Toll‐like receptor 9 in recipient cells, | Oncogene | 43 |
Abbreviations: EGFR, epidermal growth factor receptor; ESCC, esophageal squamous cell carcinoma; HCC, human hepatocellular carcinoma; ROS, reactive oxygen species.