| Literature DB >> 27396341 |
Tim N Beck1, Vladislav A Korobeynikov2, Alexander E Kudinov3, Rachel Georgopoulos4, Nehal R Solanki5, Magda Andrews-Hoke6, Timothy M Kistner7, David Pépin8, Patricia K Donahoe8, Emmanuelle Nicolas3, Margret B Einarson3, Yan Zhou9, Yanis Boumber3, David A Proia10, Ilya G Serebriiskii11, Erica A Golemis12.
Abstract
Anti-Müllerian hormone (AMH) and its type II receptor AMHR2, both previously thought to primarily function in gonadal tissue, were unexpectedly identified as potent regulators of transforming growth factor (TGF-β)/bone morphogenetic protein (BMP) signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-β/BMP superfamily member, and AMHR2 heterodimerizes with type I receptors (ALK2, ALK3) also used by the type II receptor for BMP (BMPR2). AMH signaling regulates expression of BMPR2, ALK2, and ALK3, supports protein kinase B-nuclear factor κB (AKT-NF-κB) and SMAD survival signaling, and influences BMP-dependent signaling in non-small cell lung cancer (NSCLC). AMH and AMHR2 are selectively expressed in epithelial versus mesenchymal cells, and loss of AMH/AMHR2 induces EMT. Independent induction of EMT reduces expression of AMH and AMHR2. Importantly, EMT associated with depletion of AMH or AMHR2 results in chemoresistance but sensitizes cells to the heat shock protein 90 (HSP90) inhibitor ganetespib. Recognition of this AMH/AMHR2 axis helps to further elucidate TGF-β/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT.Entities:
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Year: 2016 PMID： 27396341 PMCID： PMC4956518 DOI： 10.1016/j.celrep.2016.06.043
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423