Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis

Ching Chieh Weng, Pei Ya Ding, Yu Hsuan Liu, John R. Hawse, Malayannan Subramaniam, Chia Chen Wu, Yu Chun Lin, Chiao Yun Chen, Wen Chun Hung, Kuang Hung Cheng

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Prostate cancer (PCA), one of the most common malignant tumors in men, is the second leading cause of cancer deaths in males worldwide. We report here that PCA models harboring conditional LSL/Kras G12D or BRAF F-V600E allele with prostate-specific abrogated p53 function recapitulate human PCA precursor lesions, histopathology, and clinical behaviors. We found that the development of reprogrammed EMT-like phenotypes and skeleton metastatic behavior requires concurrent activated Kras and p53 depletion in PCA. Microarray analyses of primary PCA cells derived from these models identified several cancer stemness genes including CD24, EpCAM, and CD133 upregulated by KRAS G12D . Among these stemness markers, we identified CD24 as a key driver of tumorigenesis and metastasis in vivo. These data demonstrate that specific factors involved in cancer stemness are critical for metastatic conversion of PCA and may be ideal targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)2005-2019
Number of pages15
JournalOncogene
Volume38
Issue number12
DOIs
StatePublished - Mar 21 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis'. Together they form a unique fingerprint.

  • Cite this

    Weng, C. C., Ding, P. Y., Liu, Y. H., Hawse, J. R., Subramaniam, M., Wu, C. C., Lin, Y. C., Chen, C. Y., Hung, W. C., & Cheng, K. H. (2019). Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis. Oncogene, 38(12), 2005-2019. https://doi.org/10.1038/s41388-018-0575-7