MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma

Pei-Feng Liu1,2,3, Chun-Feng Chen4,5, Luo-Ping Ger6

  • 1Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

Insights

Mitogen-activated protein kinase kinase kinase 11 (MAP3K11) phosphorylates Autophagy-related 4B (ATG4B), promoting autophagy and oral cancer progression. MAP3K11 and ATG4B expression correlate with poor survival in oral squamous cell carcinoma patients.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Autophagy-related 4B (ATG4B) is crucial for autophagy, and its phosphorylation correlates with poor cancer prognosis.
  • The upstream kinases regulating ATG4B phosphorylation and their clinical relevance remain largely unknown.

Purpose of the Study:

  • To identify kinases phosphorylating ATG4B and investigate their role in oral cancer.
  • To explore the clinical significance of MAP3K11 and ATG4B in oral squamous cell carcinoma (OSCC).

Main Methods:

  • siRNA library screening to identify ATG4B-phosphorylating kinases.
  • In vitro assays using oral cancer cells to assess MAP3K11's effect on ATG4B, autophagy, and cell behavior.
  • In vivo studies using xenograft models.
  • Analysis of MAP3K11 and ATG4B protein levels in patient tumor tissues (OSCC, BMSCC, TSCC).

Main Results:

  • MAP3K11 was identified as a kinase that phosphorylates ATG4B, enhancing its activity and autophagic flux.
  • MAP3K11 ablation inhibited oral cancer cell growth, migration, invasion, and in vivo tumor growth.
  • Elevated MAP3K11 levels were observed in OSCC tissues and correlated positively with ATG4B and phosphorylated ATG4B.
  • High coexpression of MAP3K11 and ATG4B was linked to poor survival in OSCC patients.

Conclusions:

  • MAP3K11 promotes oral cancer malignancy by activating ATG4B and enhancing autophagy.
  • MAP3K11 expression is associated with poor patient survival in OSCC.
  • MAP3K11 represents a potential theranostic target for oral squamous cell carcinoma.

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