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

被引：45

作者：

Beck, Tim N. ^{[1
,2
]}

Korobeynikov, Vladislav A. ^{[1
,3
]}

Kudinov, Alexander E. ^{[1
]}

Georgopoulos, Rachel ^{[4
]}

Solanki, Nehal R. ^{[5
,6
]}

Andrews-Hoke, Magda ^{[7
]}

Kistner, Timothy M. ^{[8
]}

Pepin, David ^{[9
,10
]}

Donahoe, Patricia K. ^{[9
,10
]}

Nicolas, Emmanuelle ^{[1
]}

Einarson, Margret B. ^{[1
]}

Zhou, Yan ^{[11
]}

Boumber, Yanis ^{[1
]}

Proia, David A. ^{[12
]}

Serebriiskii, Ilya G. ^{[1
,13
]}

Golemis, Erica A. ^{[1
,2
]}

机构：

[1] Fox Chase Canc Ctr, Program Mol Therapeut, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[2] Drexel Univ, Coll Med, Program Mol & Cell Biol & Genet, Philadelphia, PA 19129 USA

[3] Novosibirsk State Univ, Dept Med, Novosibirsk 630090, Russia

[4] Temple Univ, Sch Med, Philadelphia, PA 19140 USA

[5] Fox Chase Canc Ctr, Immune Cell Dev & Host Def Program, Philadelphia, PA 19111 USA

[6] Drexel Univ, Coll Med, Program Microbiol & Immunol, Philadelphia, PA 19129 USA

[7] Yale Univ, New Haven, CT 06520 USA

[8] Johns Hopkins Univ, Baltimore, MD 21218 USA

[9] Harvard Med Sch, Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA

[10] Harvard Med Sch, Dept Surg, Boston, MA 02114 USA

[11] Fox Chase Canc Ctr, Dept Biostat & Bioinformat, Philadelphia, PA 19140 USA

[12] Synta Pharmaceut, Lexington, MA 02421 USA

[13] Kazan Fed Univ, Kazan 420000, Russia

来源：

CELL REPORTS | 2016年 / 16卷 / 03期

关键词：

TO-MESENCHYMAL TRANSITION; TGF-BETA; INHIBITING SUBSTANCE; OVARIAN-CANCER; II RECEPTOR; STEM-CELLS; PATHWAY; ADENOCARCINOMA; PROGRESSION; ACTIVATION;

D O I：

10.1016/j.celrep.2016.06.043

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Anti-Mullerian 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-beta)/bone morphogenetic protein (BMP) signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-beta/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 kappa B (AKTNF-kappa B) 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-beta/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT.

引用

页码：657 / 671

页数：15

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