HSPB1 inhibits the endothelial-to-mesenchymal transition to suppress pulmonary fibrosis and lung tumorigenesis

Seo Hyun Choi, Jae Kyung Nam, Bu Yeo Kim, Junho Jang, Young Bae Jin, Hae June Lee, Seungwoo Park, Young Hoon Ji, Jaeho Cho, Yoon Jin Lee

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27 Citations (Scopus)

Abstract

The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFβ or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non-small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases.

Original languageEnglish
Pages (from-to)1019-1030
Number of pages12
JournalCancer Research
Volume76
Issue number5
DOIs
Publication statusPublished - 2016 Mar 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Choi, S. H., Nam, J. K., Kim, B. Y., Jang, J., Jin, Y. B., Lee, H. J., Park, S., Ji, Y. H., Cho, J., & Lee, Y. J. (2016). HSPB1 inhibits the endothelial-to-mesenchymal transition to suppress pulmonary fibrosis and lung tumorigenesis. Cancer Research, 76(5), 1019-1030. https://doi.org/10.1158/0008-5472.CAN-15-0952