Cancerous Protein Network That Inhibits the Tumor Suppressor Function of WW Domain-Containing Oxidoreductase (WWOX)
Chiemi Saigo1, Yusuke Kito1, Tamotsu Takeuchi1
1Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.
Abstract:
Recent findings indicate that the WW domain-containing oxidoreductase (WWOX) is a tumor suppressor protein that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase domain. WWOX protein mediates multiple signaling networks that suppress carcinogenesis through binding of its first WW domain to various cancer-associated proteins, i.e., p73, AP-2γ, and others. Although the tumor suppressor property of WWOX is inarguable, WWOX is not inactivated in the manner characteristic of the canonical Knudson hypothesis. Impairment of both alleles of WWOX is thought to be a rare event, only occurring in a few cancer cell lines. How is the tumor suppressor function of WWOX impaired in cancer cells? Recent advances highlight that a small transmembrane protein possessing a PPxY motif, called TMEM207, and its relatives are aberrantly expressed in various cancer cells and hinder the tumor suppressor function of WWOX through inhibiting its WW domain. Here, we review the recent findings related to the pathobiological properties of TMEM207 and its relatives based on clinicopathological and experimental pathological studies.
Insights
The WW domain-containing oxidoreductase (WWOX) suppresses tumors by interacting with cancer proteins. Aberrant expression of TMEM207 hinders WWOX function, impacting cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- WW domain-containing oxidoreductase (WWOX) is a tumor suppressor protein.
- WWOX contains WW domains and a short-chain dehydrogenase/reductase domain, mediating anti-carcinogenesis signaling.
- Canonical Knudson hypothesis inactivation is rare for WWOX; its tumor suppressor role impairment mechanism is unclear.
Purpose of the Study:
- To review recent findings on the pathobiological properties of TMEM207 and its relatives.
- To elucidate how TMEM207 and related proteins impair WWOX tumor suppressor function in cancer cells.
Main Methods:
- Review of clinicopathological studies.
- Analysis of experimental pathological studies.
- Examination of molecular interactions between TMEM207 and WWOX.
Main Results:
- TMEM207 and relatives are aberrantly expressed in various cancer cells.
- These proteins inhibit WWOX's tumor suppressor function by hindering its WW domain.
- WWOX inactivation in cancer may not follow the typical two-hit hypothesis.
Conclusions:
- TMEM207 and its relatives represent a novel mechanism for WWOX functional impairment in cancer.
- Understanding TMEM207's role offers potential new therapeutic targets for cancer treatment.
- Further research into TMEM207 pathobiology is warranted.
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