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Updated: May 6, 2026
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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
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SH3RF2 functions as an oncogene by mediating PAK4 protein stability
Tae Woo Kim1, Yun Kyung Kang, Zee Yong Park
1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Carcinogenesis
|October 17, 2013
Summary
SH3RF2 is an oncogene overexpressed in cancers, promoting cell survival by stabilizing PAK4. Inhibiting SH3RF2 may offer a new therapeutic strategy for cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- SH3RF proteins are involved in cell survival and apoptosis.
- SH3RF2 is identified as a potential oncogene.
Purpose of the Study:
- To investigate the role of SH3RF2 in human cancers.
- To elucidate the mechanism by which SH3RF2 regulates protein stability and cell signaling.
Main Methods:
- Immunohistochemical analysis of 159 colon cancer tissues.
- Investigation of SH3RF2's effect on PAK4 protein stability and ubiquitination.
- Analysis of downstream signaling pathways, including TNF-α, TRADD, NF-κB, and caspase-8.
- In vivo and in vitro experiments assessing cell migration, apoptosis, and tumor growth.
Main Results:
- SH3RF2 is overexpressed in colon cancer tissues and correlates with poor prognosis.
- SH3RF2 inhibits PAK4 ubiquitination and degradation, leading to PAK4 upregulation.
- SH3RF2 ablation affects TNF-α signaling, inhibiting NF-κB and enhancing caspase-8 activity.
- Ectopic SH3RF2 expression promotes cancer cell survival, migration, colony formation, and tumor growth.
Conclusions:
- SH3RF2 functions as an oncogene by regulating PAK4 stability.
- SH3RF2 plays a significant role in cancer progression and survival.
- SH3RF2 represents a potential therapeutic target for cancer treatment.
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