Pivotal role of augmented αb-crystallin in tumor development induced by deficient TSC1/2 complex

F. Wang, X. Chen, C. Li, Q. Sun, Y. Chen, Y. Wang, H. Peng, Z. Liu, R. Chen, K. Liu, H. Yan, B. H. Ye, D. J. Kwiatkowski, H. Zhang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Tuberous sclerosis complex 1 (TSC1) and TSC2 are suppressors of mechanistic target of rapamycin (mTOR). mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2. Inactive mutation of either TSC1 or TSC2 unleashes mTOR signaling and consequently causes TSC, a benign tumor syndrome affecting multiple organs. We report here that expression of αB-crystallin was upregulated in Tsc1-/- or Tsc2-/- mouse embryonic fibroblasts, Eker rat uterine leiomyoma-derived Tsc2-deficient ELT3 cells, mutant Tsc2-associated mouse kidney tumors, and human lung lymphangioleiomyomatosis nodules. αB-crystallin was transcriptionally activated by mTOR complex 2 (mTORC2): nuclear factor-kappa B (NFκB) signaling cascade. The augmented αB-crystallin was critical for the migration, invasion and apoptotic resistance of Tsc2-defective cells. Disruption of αB-crystallin suppressed Tsc2-null cell proliferation and tumorigenesis. Therefore, enhanced αB-crystallin has an essential role in TSC1/2 complex deficiency-mediated tumorigenesis, and inhibition of αB-crystallin may complement the current therapy for TSC.

Original languageEnglish (US)
Pages (from-to)4352-4358
Number of pages7
JournalOncogene
Volume33
Issue number34
DOIs
StatePublished - Aug 21 2014

Keywords

  • NFκB
  • TSC
  • mTOR
  • tumor
  • αB-crystallin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Pivotal role of augmented αb-crystallin in tumor development induced by deficient TSC1/2 complex'. Together they form a unique fingerprint.

  • Cite this

    Wang, F., Chen, X., Li, C., Sun, Q., Chen, Y., Wang, Y., Peng, H., Liu, Z., Chen, R., Liu, K., Yan, H., Ye, B. H., Kwiatkowski, D. J., & Zhang, H. (2014). Pivotal role of augmented αb-crystallin in tumor development induced by deficient TSC1/2 complex. Oncogene, 33(34), 4352-4358. https://doi.org/10.1038/onc.2013.401