Heat shock protein 47 (HSP47) binds to discoidin domain-containing receptor 2 (DDR2) and regulates its protein stability

Jie Chen, Shike Wang, Zhihui Zhang, Christopher I. Richards, Ren Xu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Cell- collagen interactions are crucial for cell migration and invasion during cancer development and progression. Heat shock protein 47 (HSP47) is an endoplasmic reticulum-resident molecular chaperone that facilitates collagen maturation and deposition. It has been previously shown that HSP47 expression in cancer cells is crucial for cancer invasiveness. However, exogenous collagen cannot rescue cell invasion in HSP47-silenced cancer cells, suggesting that other HSP47 targets contribute to cancer cell invasion. Here, we show that HSP47 expression is required for the stability and cell-surface expression of discoidin domain-containing receptor 2 (DDR2) in breast cancer tissues. HSP47 silencing reduced DDR2 protein stability, accompanied by suppressed cell migration and invasion. Coimmunoprecipitation results revealed that HSP47 binds to the DDR2 ectodomain. Using a photoconvertible technique and total internal reflection fluorescence microscopy, we further demonstrate that HSP47 expression significantly sustains the membrane localization of the DDR2 protein. These results suggest that binding of HSP47 to DDR2 increases DDR2 stability and regulates its membrane dynamics and thereby enhances cancer cell migration and invasion. Given that DDR2 has a crucial role in the epithelial-to-mesenchymal transition and cancer progression, targeting the HSP47-DDR2 interaction might be a potential strategy for inhibiting DDR2-dependent cancer progression.

Original languageEnglish
Pages (from-to)16846-16854
Number of pages9
JournalJournal of Biological Chemistry
Issue number45
StatePublished - Nov 8 2019

Bibliographical note

Publisher Copyright:
© 2019 Chen et al.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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