Functional impact of cancer patient‐associated Bcl‐xL mutations
Abstract
Bcl‐xL, an antiapoptotic protein, is frequently overexpressed in cancer to promote survival of tumor cells. However, we have previously shown that Bcl‐xL promotes migration, invasion, and metastasis independent of its antiapoptotic function in mitochondria. The pro‐metastatic function of Bcl‐xL may require its translocation into the nucleus. Besides overexpression, patient‐associated mutations of Bcl‐xL have been identified in large‐scale cancer genomics projects. Understanding the functions of these mutations will guide the development of precision medicine. Here, we selected four patient‐associated Bcl‐xL mutations, R132W, N136K, R165W, and A201T, to investigate their impacts on antiapoptosis, migration, and nuclear translocation. We found that all four mutation proteins could be detected in both the nucleus and cytosol. Although all four mutations disrupted the antiapoptosis function, one of these mutants, N136K, significantly improved the ability to promote cell migration. These data suggest the importance of developing novel Bcl‐xL inhibitors to ablate both antiapoptotic and pro‐metastatic functions of Bcl‐xL in cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 29, 2020
- Source ID
- 10.1002/mco2.36
Entities
People
- Anthony F. Daniyan
- George Zhang
- Joseph Na
- Lei Shi
- Samantha Li
- Sharon Pang
- Tiantian Zhang
- Yi Li
- Yi‐chieh Nancy Du
- Zhengming Chen
Organizations
- Baylor College of Medicine
- Memorial Sloan Kettering Cancer Center
- National Institute on Drug Abuse
- National Institutes of Health
- The Starr Foundation
- United States Department of Defense
- Weill Cornell Medicine