Rare Diseases Symptoms Automatic Extraction

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

[lymphangioleiomyomatosis]

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.

Diseases presenting "multiple organs" symptom

  • cowden syndrome
  • cutaneous mastocytosis
  • erdheim-chester disease
  • fabry disease
  • holt-oram syndrome
  • kabuki syndrome
  • lamellar ichthyosis
  • lymphangioleiomyomatosis
  • malignant atrophic papulosis
  • oculocutaneous albinism
  • primary hyperoxaluria type 1
  • pyomyositis
  • scrub typhus

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