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Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer
Journal article   Open access   Peer reviewed

Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer

Tim N Beck, Vladislav A Korobeynikov, Alexander E Kudinov, Rachel Georgopoulos, Nehal R Solanki, Magda Andrews-Hoke, Timothy M Kistner, David Pépin, Patricia K Donahoe, Emmanuelle Nicolas, …
Cell reports (Cambridge), v 16(3), pp 657-671
19 Jul 2016
DOI: https://doi.org/10.1016/j.celrep.2016.06.043
PMID: 27396341
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.cell.com/article/S2211124716307975/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1016/j.celrep.2016.06.043View
Published, Version of Record (VoR) Open

Abstract

Animals Anti-Mullerian Hormone - metabolism Bone Morphogenetic Protein Receptors, Type II - metabolism Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Cell Plasticity - physiology Drug Resistance, Neoplasm - physiology Epithelial Cells - metabolism Epithelial Cells - physiology Epithelial-Mesenchymal Transition - physiology Gene Expression Regulation - physiology Heat-Shock Proteins - metabolism Lung Neoplasms - metabolism Lung Neoplasms - pathology Mesenchymal Stromal Cells - metabolism Mesenchymal Stromal Cells - pathology Mice Mice, SCID NF-kappa B - metabolism Receptors, Peptide - metabolism Receptors, Transforming Growth Factor beta - metabolism Signal Transduction - physiology Transforming Growth Factor beta - metabolism
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.

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50 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Web of Science research areas
Cell Biology
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