TY - JOUR
T1 - Regulation of cell signaling and apoptosis by tumor suppressor WWOX
AU - Lo, Jui Yen
AU - Chou, Ying Tsen
AU - Lai, Feng Jie
AU - Hsu, Li Jin
N1 - Funding Information:
This manuscript was supported by the Ministry of Science and Technology, Taiwan, grants 101-2320-B-006-032-MY3, 102-2320-B-006-019, and 103-2320-B-006-002 to LJH and Chi Mei Hospital and National Cheng Kung University Collaborative Research grants CMNCKU10204 and CMNCKU10302 to FJL and LJH.
Publisher Copyright:
© 2015 by the Society for Experimental Biology and Medicine
PY - 2015/3/25
Y1 - 2015/3/25
N2 - 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.
AB - 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.
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U2 - 10.1177/1535370214566747
DO - 10.1177/1535370214566747
M3 - Article
C2 - 25595191
AN - SCOPUS:84925325139
VL - 240
SP - 383
EP - 391
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 1535-3702
IS - 3
ER -