Regulation of cell signaling and apoptosis by tumor suppressor WWOX

Jui Yen Lo, Ying Tsen Chou, Feng Jie Lai, Li Jin Hsu

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell death induced by a variety of stress stimuli, such as tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Loss of WWOX gene expression due to gene deletions, loss of heterozygosity, chromosomal translocations, or epigenetic silencing is frequently observed in human malignant cancer cells. Acquisition of chemoresistance in squamous cell carcinoma, osteosarcoma, and breast cancer cells is associated with WWOX deficiency. WWOX protein physically interacts with many signaling molecules and exerts its regulatory effects on gene transcription and protein stability and subcellular localization to control cell survival, proliferation, differentiation, autophagy, and metabolism. In this review, we provide an overview of the recent advances in understanding the molecular mechanisms by which WWOX regulates cellular functions and stress responses. A potential scenario is that activation of WWOX by anticancer drugs is needed to overcome chemoresistance and trigger cancer cell death, suggesting that WWOX can be regarded as a prognostic marker and a candidate molecule for targeted cancer therapies.

Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalExperimental Biology and Medicine
Issue number3
Publication statusPublished - 2015 Mar 25

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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