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.