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TRIM50 acts as a novel Src suppressor and inhibits ovarian cancer progression

Yumin Qiu1, Peishu Liu2, Xiaomin Ma3

  • 1Department of Immunology, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Basic Medical Sciences, 250012 Jinan, China; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan 250012, Shandong Province, China.

Biochimica Et Biophysica Acta. Molecular Cell Research
|June 10, 2019
PubMed

Insights

Tripartite motif-containing (TRIM) 50 suppresses ovarian cancer by inhibiting Src protein activity. TRIM50 reduces Src stability and tumor growth, offering a potential therapeutic strategy for cancers with high Src activity.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Src is a proto-oncogene implicated in various cancers, including ovarian cancer.
  • The precise regulatory mechanisms governing Src activity remain incompletely understood.
  • Understanding Src regulation is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To identify novel regulators of Src protein.
  • To investigate the role of tripartite motif-containing (TRIM) 50 in ovarian cancer.
  • To elucidate the mechanism by which TRIM50 affects Src activity and ovarian cancer progression.

Main Methods:

  • Protein-protein interaction assays to confirm TRIM50 and Src binding.
  • Ubiquitination assays to assess Src protein stability.
  • In vitro studies using ovarian cancer cell lines.
  • In vivo xenograft models to evaluate tumor growth inhibition.
  • Analysis of clinical specimens to correlate TRIM50 expression with disease parameters.

Main Results:

  • TRIM50 directly interacts with the Src SH3 domain via its B-box domain.
  • TRIM50 reduces Src protein stability through K48-linked poly-ubiquitination, dependent on its RING domain.
  • TRIM50 suppresses ovarian cancer cell proliferation and xenograft tumor growth by inhibiting Src.
  • TRIM50 expression inversely correlates with advanced clinical stages, higher grades, and lymph node metastasis in ovarian cancer patients.
  • A negative correlation between TRIM50 and Src expression was observed in clinical specimens.

Conclusions:

  • TRIM50 is identified as a novel negative regulator of Src protein.
  • TRIM50 functions as a tumor suppressor in ovarian cancer by targeting Src.
  • TRIM50 inhibits ovarian cancer progression by reducing Src activity, presenting a potential therapeutic target for Src-driven cancers.
Keywords:
Ovarian cancerSrcTRIM50Tumor suppressorUbiquitination

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