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SHARPIN overexpression promotes TAK1 expression and activates JNKs and NF-κB pathway in Mycosis Fungoides

Biao Chen1, Yan Zheng1, Jingna Zhu1

  • 1Department of Dermatology, Cosmetology and Venereology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Experimental Dermatology
|August 29, 2019
PubMed

Insights

Shank-associated RH domain-interacting protein (SHARPIN) upregulation correlates with poor prognosis in Mycosis Fungoides (MF), a type of cutaneous T-cell lymphoma (CTCL). SHARPIN activates key signaling pathways, promoting MF cell growth and spread.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL).
  • Shank-associated RH domain-interacting protein (SHARPIN) is implicated in tumor development, but its role in MF is unknown.
  • The c-Jun N-terminal kinases (JNKs) pathway is dysregulated in CTCL, yet its specific role in MF and its relationship with SHARPIN remain unclear.

Purpose of the Study:

  • To investigate the clinical significance of SHARPIN in MF.
  • To elucidate the relationship between SHARPIN and the JNKs pathway in MF.
  • To determine the molecular mechanisms by which SHARPIN influences MF progression.

Main Methods:

  • Analysis of SHARPIN expression in MF patients and correlation with prognosis.
  • In vitro studies using the MF cell line MyLa2059.
  • Investigation of SHARPIN's effects on signaling pathways including JNKs, NF-κB, p38, and TAK1.

Main Results:

  • Upregulated SHARPIN expression is associated with poor prognosis in MF patients.
  • SHARPIN expression and JNKs pathway activation are increased in MF cells (MyLa2059).
  • SHARPIN induces transforming growth factor β activated kinase-1 (TAK1) transcription, activating JNKs and NF-κB pathways.
  • SHARPIN independently promotes p38 signaling, leading to increased cell proliferation, migration, and invasion, while inhibiting apoptosis in MyLa2059 cells.

Conclusions:

  • SHARPIN upregulation is a potential biomarker for poor prognosis in MF.
  • SHARPIN plays a significant role in MF development by activating JNKs, NF-κB, and p38 signaling pathways.
  • Targeting SHARPIN or its downstream pathways may offer therapeutic strategies for MF.
Keywords:
Mycosis Fungoidesshank-associated RH domain-interacting proteinsignalling pathwaytransforming growth factor β activated kinase-1

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