Abstract
Simple SummaryColorectal cancer is common cancer, and currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value of DJ-1 in colorectal cancer and the role of DJ-1-induced mitophagy in colorectal cancer progression. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM (tumor-node-metastasis) stage in colorectal cancer patients. Besides, DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition in metastatic colorectal adenocarcinoma cells. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.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.
Highlights
In 2020, colorectal cancer was the third most common cancer and cancer-related death in the United States [1]
DJ-1 mRNA Overexpression in Tumor Tissues (T) but Not Adjacent Normal Tissues (N) Is Positively Correlated with TNM Stages of Colorectal Cancer Patients, and DJ-1 s Function Might Associate with Autophagy/Mitophagy
Our data indicate that DJ-1 mRNA overexpression in tumor tissues is positively correlated with TNM stages of colorectal cancer patients, and its function might associate with autophagy/mitophagy
Summary
In 2020, colorectal cancer was the third most common cancer and cancer-related death in the United States [1]. In 2018, the cancer registry report of Taiwan shows that colorectal cancer was the second most common cancer and the third cancer-associated death in Taiwan [2]. About 22% of colorectal cancer patients are metastatic at initial diagnosis, and the patients with metastatic colorectal cancer face a poor prognosis and have a relative 5-year survival rate of 14% [4]. A study shows that the five-year recurrence rates in 871 TNM stage II and 265 TNM stage III colon cancer patients were 10% and 30%, respectively [3]. The median overall survival of patients with metastatic colorectal cancer was about 30 months in recent clinical trials of first-line therapies [5]. Early detection of colorectal cancer and elucidating detailed mechanisms underlying cancer progression are required to provide more reliable molecular targets for therapy and improve colorectal cancer prognoses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
