Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/β-catenin signaling

Kuangen Zhang1,2, Rui Wu1, Fang Mei1

  • 1Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Insights

The tumor suppressor LASS2 degrades beta-catenin, inhibiting prostate cancer. Phosphorylation of LASS2 at serine 248 is crucial for this function, suggesting LASS2 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • LASS2, a novel tumor suppressor, functions as a ceramide synthase.
  • Its role in prostate carcinogenesis and associated pathways remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the function and pathway-related activity of LASS2 in prostate cancer.
  • To investigate the mechanism by which LASS2 regulates prostate carcinogenesis.

Main Methods:

  • Investigated LASS2's interaction with STK38, SCYL2, and ATP6V0C.
  • Utilized the ubiquitin-proteasome pathway to study beta-catenin degradation.
  • Identified serine residue 248 as a key phosphorylation site on LASS2.

Main Results:

  • LASS2 promotes beta-catenin degradation via physical interaction with STK38, SCYL2, and ATP6V0C.
  • Phosphorylation of LASS2, particularly at serine 248, is essential for beta-catenin degradation.
  • Dephosphorylation of LASS2 at serine 248 enhances prostate cancer cell growth and metastasis in vivo.

Conclusions:

  • Phosphorylated LASS2 inhibits prostate carcinogenesis by negatively regulating the Wnt/beta-catenin signaling pathway.
  • LASS2 plays a critical role in suppressing prostate cancer progression.
  • LASS2 represents a potential biomarker and therapeutic target for prostate cancer.

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