ArticleCancer cell international2023
ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 8 citations in OpenAlex.
- Review
- Autophagy Protease ATG4D Facilitates Proliferation and Malignancy of Osteosarcoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Evaluation of autophagy related ATG4B gene, protein and miR-655-3p expression levels in endometrial cancer and hyperplasia.Journal of gynecologic oncology · 2025Article
- Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases.World journal of gastroenterology · 2024Review
- Biologic activity and treatment resistance to gastrointestinal cancer: the role of circular RNA in autophagy regulation.Frontiers in oncology · 2024Review
- The dual role of autophagy in suppressing and promoting hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
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10 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundAutophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression. Phosphorylation of ATG4B is crucial for activation of its protease activity. However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).
methodsThe ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays.
resultsATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells.
conclusionsOur results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.
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