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Phosphorylation of ATG4B promotes autophagy and is correlated with poor outcome of cancer. However, little is known about the upstream kinases for ATG4B phosphorylation and their association with clinical outcomes of cancer patients.\u00a0Through siRNA library screening, MAP3K11 was identified as a potential kinase that phosphorylates ATG4B and increases its proteolytic activity. Ablation of MAP3K11 attenuated pS383\/392\u2010ATG4B protein levels and autophagic flux in oral cancer cells. Moreover, loss of MAP3K11 inhibited oral cancer cell growth, migration\/invasion, and synergized starvation\u2010reduced cell viability. MAP3K11\u00a0knock\u2010out cancer cells also showed growth inhibition in vivo. Furthermore, the protein level of MAP3K11 was higher in tumor tissues than that in adjacent normal tissues in patients with oral squamous cell carcinoma (OSCC), comprising 179 buccal mucosa squamous cell carcinoma (BMSCC) and 249 tongue squamous cell carcinoma (TSCC). MAP3K11 protein levels were positively correlated with ATG4B and pS383\/392\u2010ATG4B levels in patients with OSCC, particularly in TSCC. In addition, high coexpression of MAP3K11 and ATG4B was associated with poor disease\u2010specific survival in BMSCC and TSCC, while high coexpression of MAP3K11 and pS383\/392\u2010ATG4B was associated with unfavorable disease\u2010free survival in BMSCC and TSCC. Taken together, our results indicated that MAP3K11 stimulated activity of ATG4B and autophagy, which may confer to malignancy of cancer cells. The expression of MAP3K11 and ATG4B was further associated with poor survival of OSCC, suggesting MAP3K11 could serve as a theranostic target of patients with OSCC.<\/jats:p>","DOI":"10.1002\/jcp.30881","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T16:55:31Z","timestamp":1663174531000},"page":"4275-4291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma"],"prefix":"10.1002","volume":"237","author":[{"given":"Pei\u2010Feng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Environmental Biology, College of Life Science Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan"},{"name":"Center for Cancer Research Kaohsiung Medical University 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