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Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer.
Beck, Tim N; Korobeynikov, Vladislav A; Kudinov, Alexander E; Georgopoulos, Rachel; Solanki, Nehal R; Andrews-Hoke, Magda; Kistner, Timothy M; Pépin, David; Donahoe, Patricia K; Nicolas, Emmanuelle; Einarson, Margret B; Zhou, Yan; Boumber, Yanis; Proia, David A; Serebriiskii, Ilya G; Golemis, Erica A.
Afiliación
  • Beck TN; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
  • Korobeynikov VA; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Medical Department, Novosibirsk State University, Novosibirsk 630090, Russia.
  • Kudinov AE; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Georgopoulos R; Temple University School of Medicine, Philadelphia, PA 19140, USA.
  • Solanki NR; Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Program in Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
  • Andrews-Hoke M; Yale University, New Haven, CT 06520, USA.
  • Kistner TM; Johns Hopkins University, Baltimore, MD 21218, USA.
  • Pépin D; Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
  • Donahoe PK; Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
  • Nicolas E; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Einarson MB; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Zhou Y; Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA 19140, USA.
  • Boumber Y; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Proia DA; Synta Pharmaceuticals, Lexington, MA 02421, USA.
  • Serebriiskii IG; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Kazan Federal University, 420000 Kazan, Russian Federation.
  • Golemis EA; Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Electronic address: erica.golemis@fccc.edu.
Cell Rep ; 16(3): 657-71, 2016 07 19.
Article en En | MEDLINE | ID: mdl-27396341
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-ß)/bone morphogenetic protein (BMP) signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-ß/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-ß/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Antineoplásicos / Células Epiteliales / Hormona Antimülleriana / Plasticidad de la Célula / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Antineoplásicos / Células Epiteliales / Hormona Antimülleriana / Plasticidad de la Célula / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos