Fam20C regulates bone resorption and breast cancer bone metastasis through osteopontin and BMP4

Hao Zuo, Dengbao Yang, Yihong Wan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Fam20C is a kinase that generates the majority of secreted phosphoproteins and regulates biomineralization. However, its potential roles in bone resorption and breast cancer bone metastasis are unknown. Here we show that Fam20C in the myeloid lineage suppresses osteoclastogenesis and bone resorption, during which osteopontin (OPN) is the most abundant phosphoprotein secreted in a Fam20C-dependent manner. OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C-deficiency-induced osteoclast differentiation and bone metastasis. In contrast, Fam20C in breast cancer cells promoted bone metastasis by facilitating the phosphorylation and secretion of BMP4, which in turn enhanced osteoclastogenesis. Mutation of the BMP4 phosphorylation site elevated BMP4 lysosomal degradation and reduced BMP4 secretion. In breast cancer cells, BMP4 depletion or treatment with a BMP4 signaling inhibitor diminished osteoclast differentiation and bone metastasis and abolished Fam20C-mediated regulation of these processes. Collectively, this study discovers distinct roles for Fam20C in myeloid cells and breast cancer cells and highlights OPN and BMP4 as potential therapeutic targets for breast cancer bone metastasis.

Original languageEnglish (US)
JournalCancer research
Volume81
Issue number20
DOIs
StatePublished - Oct 15 2021

Keywords

  • Bone metastasis
  • Bone resorption
  • Breast cancer
  • Fam20C
  • Osteoclast

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Fam20C regulates bone resorption and breast cancer bone metastasis through osteopontin and BMP4'. Together they form a unique fingerprint.

Cite this