Colorectal cancer is the second most common
cancer and the third
cancer-associated death in Taiwan. Currently used
serum markers for detecting
colorectal cancer lack excellent diagnostic accuracy, which results in
colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an
antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-
cancer drug resistance. However, the role of DJ-1-induced mitophagy in
colorectal cancer progression remains unclear. In the present study, we collected matched
tumor and adjacent normal tissues and serum from patients and
cancer cells to demonstrate the clinical value and physiological function of DJ-1 in
colorectal cancer. We found that DJ-1 increased in
tumor tissues and serum; it was positively correlated with TNM (
tumor-node-
metastasis) stages of
colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal
adenocarcinoma cells SW620, DJ-1 knockdown inhibited
cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect
ATP production; DJ-1 knockdown enhanced intracellular
reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal
adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance
cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue
biomarkers for predicting the TNM stage in
colorectal cancer patients. Since DJ-1-induced mitophagy promotes
tumor progression, DJ-1 inhibition is a potential therapeutic strategy for
colorectal cancer treatment.