The paracrine induction of prostate cancer progression by caveolin-1

Chun Jung Lin, Eun Jin Yun, U. Ging Lo, Yu Ling Tai, Su Deng, Elizabeth Hernandez, Andrew Dang, Yu An Chen, Debabrata Saha, Ping Mu, Ho Lin, Tsai Kun Li, Tang Long Shen, Chih Ho Lai, Jer Tsong Hsieh

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Abstract

A subpopulation of cancer stem cells (CSCs) plays a critical role of cancer progression, recurrence, and therapeutic resistance. Many studies have indicated that castration-resistant prostate cancer (CRPC) is associated with stem cell phenotypes, which could further promote neuroendocrine transdifferentiation. Although only a small subset of genetically pre-programmed cells in each organ has stem cell capability, CSCs appear to be inducible among a heterogeneous cancer cell population. However, the inductive mechanism(s) leading to the emergence of these CSCs are not fully understood in CRPC. Tumor cells actively produce, release, and utilize exosomes to promote cancer development and metastasis, cancer immune evasion as well as chemotherapeutic resistance; the impact of tumor-derived exosomes (TDE) and its cargo on prostate cancer (PCa) development is still unclear. In this study, we demonstrate that the presence of Cav-1 in TDE acts as a potent driver to induce CSC phenotypes and epithelial–mesenchymal transition in PCa undergoing neuroendocrine differentiation through NFκB signaling pathway. Furthermore, Cav-1 in mCRPC-derived exosomes is capable of inducing radio- and chemo-resistance in recipient cells. Collectively, these data support Cav-1 as a critical driver for mCRPC progression.

Original languageEnglish (US)
Article number834
JournalCell Death and Disease
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2019

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ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Lin, C. J., Yun, E. J., Lo, U. G., Tai, Y. L., Deng, S., Hernandez, E., Dang, A., Chen, Y. A., Saha, D., Mu, P., Lin, H., Li, T. K., Shen, T. L., Lai, C. H., & Hsieh, J. T. (2019). The paracrine induction of prostate cancer progression by caveolin-1. Cell Death and Disease, 10(11), [834]. https://doi.org/10.1038/s41419-019-2066-3