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Fbw7 regulates apoptosis in activated B-cell like diffuse large B-cell lymphoma by targeting Stat3 for ubiquitylation

Su Yao1, Fangping Xu1, Yu Chen1

  • 1Department of Pathology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.

Journal of Experimental & Clinical Cancer Research : CR
|January 11, 2017
PubMed
Abstract

Insights

The tumor suppressor Fbw7 targets Stat3 for degradation, inducing apoptosis in activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL). This finding suggests Stat3 inhibition as a potential therapy for ABC-DLBCL.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Fbw7 is a ubiquitin ligase functioning as a tumor suppressor by degrading proto-oncogenes.
  • The role of Fbw7 in diffuse large B-cell lymphoma (DLBCL) pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the expression and function of Fbw7 in DLBCL.
  • To elucidate the mechanism by which Fbw7 influences DLBCL development, particularly in the activated B-cell (ABC) subtype.

Main Methods:

  • Immunohistochemical staining of Fbw7 in DLBCL patient samples.
  • Fbw7 overexpression experiments in ABC-DLBCL cell lines (SU-DHL-2, OCI-LY-3).
  • Mechanism studies using immunoprecipitation, ubiquitination assays, and western blotting.

Main Results:

  • Reduced Fbw7 expression observed in non-germinal center B-cell-like DLBCL, correlating with poorer prognosis.
  • Fbw7 overexpression decreased cell viability and increased apoptosis in ABC-DLBCL cell lines.
  • Fbw7 targets Stat3 and phospho-Stat3 for ubiquitylation and degradation, reducing the expression of Stat3 downstream targets.

Conclusions:

  • Fbw7 induces apoptosis in ABC-DLBCL by targeting Stat3 for degradation.
  • Targeting Stat3 may represent a viable therapeutic strategy for ABC-DLBCL.
Keywords:
Activated B-cellApoptosisDLBCLFbw7Stat3Ubiquitylation

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