BMP2-induction of FN14 promotes protumorigenic signaling in gynecologic cancer cells

Cell Signal. 2021 Nov:87:110146. doi: 10.1016/j.cellsig.2021.110146. Epub 2021 Sep 10.

Abstract

We previously reported that bone morphogenetic protein (BMP) signaling promotes tumorigenesis in gynecologic cancer cells. BMP2 enhances proliferation of ovarian and endometrial cancer cells via c-KIT induction, and triggers epithelial-mesenchymal transition (EMT) by SNAIL and/or SLUG induction, leading to increased cell migration. However, the downstream effectors of BMP signaling in gynecological cancer cells have not been clearly elucidated. In this study, we performed RNA-sequencing of Ishikawa endometrial and SKOV3 ovarian cancer cells after BMP2 stimulation, and identified TNFRSF12A, encoding fibroblast growth factor-inducible 14 (FN14) as a common BMP2-induced gene. FN14 knockdown suppressed BMP2-induced cell proliferation and migration, confirmed by MTS and scratch assays, respectively. In addition, FN14 silencing augmented chemosensitivity of SKOV3 cells. As a downstream effector of BMP signaling, FN14 modulated both c-KIT and SNAIL expression, which are important for growth and migration of ovarian and endometrial cancer cells. These results support the notion that the tumor promoting effects of BMP signaling in gynecological cancers are partially attributed to FN14 induction.

Keywords: BMP; Endometrial cancer; FN14; Ovarian cancer; SNAIL; c-KIT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2 / pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / pathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Signal Transduction*
  • TWEAK Receptor

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • TNFRSF12A protein, human
  • TWEAK Receptor