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TRAF inhibition drives cancer cell apoptosis and improves retinoic acid sensitivity in multiple cancers models

Kun Zhong1, Xiaojun Liu1, Weihua Ding1

  • 1Medical School, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People's Republic of China.

Discover Oncology
|June 30, 2023
PubMed

Insights

This study shows that inhibiting TNF receptor-associated factors (TRAFs) enhances cancer cells

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • TNF receptor-associated factors (TRAFs) are key signaling adaptors involved in cellular pathways, survival, and cancer.
  • 13-cis-retinoic acid (RA), a vitamin A metabolite, has anti-cancer effects, but resistance limits its clinical use.
  • Understanding factors influencing RA sensitivity is crucial for improving cancer therapy.

Purpose of the Study:

  • To investigate the association between TRAF expression and retinoic acid sensitivity in various cancers.
  • To explore the therapeutic potential of combining RA with TRAF inhibition.

Main Methods:

  • Analyzed TRAF expression across TCGA cancer cohorts and cell lines.
  • Inhibited TRAF4, TRAF5, or TRAF6 in ovarian cancer and melanoma cell lines and xenografts.
  • Assessed effects on RA sensitivity, colony formation, apoptosis (procaspase 9 levels), and in vivo tumor growth.

Main Results:

  • TRAF expression levels differed significantly across cancer types.
  • Inhibiting TRAF4, TRAF5, or TRAF6 enhanced RA sensitivity and reduced colony formation in ovarian cancer and melanoma.
  • TRAF knockdown increased procaspase 9 and induced apoptosis in RA-treated cancer cells, with confirmed anti-tumor effects in vivo.

Conclusions:

  • TRAF proteins are linked to retinoic acid resistance in cancers.
  • Silencing TRAF4, TRAF5, or TRAF6 potentiates the anti-cancer effects of retinoic acid.
  • Combination therapy with retinoic acid and TRAF silencing shows promise for treating ovarian cancer and melanoma.
Keywords:
Retinoic acid sensitivityTRAF inhibitioncancer cell apoptosis

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