2. Academic Validation
  3. Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis

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

  • Oncogene. 2019 Mar;38(12):2005-2019. doi: 10.1038/s41388-018-0575-7.
Ching-Chieh Weng 1,  Pei-Ya Ding 1,  Yu-Hsuan Liu 1,  John R Hawse 2,  Malayannan Subramaniam 2,  Chia-Chen Wu 1,  Yu-Chun Lin 1,  Chiao-Yun Chen 3,  Wen-Chun Hung 4,  Kuang-Hung Cheng 5 6 7
Affiliations

Affiliations

  • 1 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
  • 2 Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.
  • 3 Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 4 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
  • 5 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan. khcheng@faculty.nsysu.edu.tw.
  • 6 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. khcheng@faculty.nsysu.edu.tw.
  • 7 Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. khcheng@faculty.nsysu.edu.tw.
PMID: 30467381 DOI: 10.1038/s41388-018-0575-7
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/KrasG12D or BRafF-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 KRASG12D. 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.

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