Activin A stimulates migration of the fallopian tube epithelium, an origin of high-grade serous ovarian cancer, through non-canonical signaling

Matthew Dean, David A. Davis, Joanna E. Burdette

Research output: Contribution to journalArticlepeer-review

Abstract

Factors that stimulate the migration of fallopian tube epithelial (FTE)-derived high-grade serous ovarian cancer (HGSOC) to the ovary are poorly elucidated. This study characterized the effect of the ovarian hormone, activin A, on normal FTE and HGSOC. Activin A and TGFβ1 induced an epithelial-to-mesenchymal transition in murine oviductal epithelial (MOE) cells, but only activin A increased migration. The migratory effect of activin A was independent of Smad2/3 and required phospho-AKT, phospho-ERK, and Rac1. Exogenous activin A stimulated migration of the HGSOC cell line OVCAR3 through a similar mechanism. Activin A signaling inhibitors, SB431542 and follistatin, reduced migration in OVCAR4 cells, which expressed activin A subunits (encoded by INHBA). Murine superovulation increased phospho-Smad2/3 immunostaining in the FTE. In Oncomine, transcripts for the activin A receptors (ACVR1B and ACVR2A) were higher in serous tumors relative to the normal ovary, while inhibitors of activin A signaling (INHA and TGFB3) were lower. High expression of both INHBA and ACVR2A, but not TGFβ receptors or co-receptors, was associated with shorter disease-free survival in serous cancer patients. These results suggest activin A stimulates migration of FTE-derived tumors to the ovary.

Original languageEnglish (US)
Pages (from-to)114-124
Number of pages11
JournalCancer Letters
Volume391
DOIs
StatePublished - Apr 10 2017
Externally publishedYes

Keywords

  • Activin
  • Fallopian tube
  • Ovarian cancer
  • Oviduct
  • Serous cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Activin A stimulates migration of the fallopian tube epithelium, an origin of high-grade serous ovarian cancer, through non-canonical signaling'. Together they form a unique fingerprint.

Cite this