| First Author | Wang F | Year | 2014 |
| Journal | Oncogene | Volume | 33 |
| Issue | 34 | Pages | 4352-8 |
| PubMed ID | 24077282 | Mgi Jnum | J:214354 |
| Mgi Id | MGI:5588796 | Doi | 10.1038/onc.2013.401 |
| Citation | Wang F, et al. (2014) Pivotal role of augmented alphaB-crystallin in tumor development induced by deficient TSC1/2 complex. Oncogene 33(34):4352-8 |
| abstractText | 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 alphaB-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. alphaB-crystallin was transcriptionally activated by mTOR complex 2 (mTORC2): nuclear factor-kappa B (NFkappaB) signaling cascade. The augmented alphaB-crystallin was critical for the migration, invasion and apoptotic resistance of Tsc2-defective cells. Disruption of alphaB-crystallin suppressed Tsc2-null cell proliferation and tumorigenesis. Therefore, enhanced alphaB-crystallin has an essential role in TSC1/2 complex deficiency-mediated tumorigenesis, and inhibition of alphaB-crystallin may complement the current therapy for TSC. |
