Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis
Abstract
The evolutionarily conserved RNA-binding protein Musashi-2 (MSI2) regulates mRNA translation and influences multiple biological processes, including maintenance of stem cell identity. This work for the first time, to our knowledge, identifies that more aggressive patient tumors have higher MSI2 levels. We define a critical role for MSI2 in supporting non-small cell lung cancer (NSCLC) invasiveness and further define claudins 3, 5, and 7 (CLDN3, CLDN5, and CLDN7), TGF-β receptor 1 (TGFβR1), and the small mothers against decapentaplegic homolog 3 (SMAD3) as targets through which MSI2 regulates this process. The observation that MSI2 expression is progressively elevated from an early stage in human NSCLC tumors suggests that this protein may play an essential role in the reprogramming of TGF-β signaling from growth-inhibiting to invasion-promoting during oncogenesis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 06, 2016
- Source ID
- 10.1073/pnas.1513616113
Entities
People
- Adaeze Chikwem
- Alexander E. Kudinov
- Alexander Y Deneka
- Anna S. Nikonova
- Brian L. Egleston
- Cathleen F. Martinez
- Don L Gibbons
- Dong-hua Yang
- Emmanuelle Nicolas
- Erica Golemis
- Fred A. Schultz
- Gregory Andrianov
- Hossein Borghaei
- Ilya G. Serebriiskii
- Jonathan M. Kurie
- Karmel A. Baker
- Kathy Q. Cai
- Khaled M. Yaghmour
- Samuel Reynolds
- Shelly Singh
- Tim N. Beck
- Xin Liu
- Yanis Boumber
- Young-Ho Ahn
Organizations
- American Cancer Society
- American Hellenic Educational Progressive Association
- Drexel University
- Ewha Womans University
- Fox Chase Cancer Center
- Kazan Federal University
- National Cancer Institute
- Temple University
- United States Department of Defense
- University of New Mexico
- University of Texas at Austin