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

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

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

Afiliación

Weng CC; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Ding PY; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Liu YH; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Hawse JR; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.
Subramaniam M; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.
Wu CC; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Lin YC; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Chen CY; Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Hung WC; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Cheng KH; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan. khcheng@faculty.nsysu.edu.tw.

Oncogene ; 38(12): 2005-2019, 2019 03.

Article en En | MEDLINE | ID: mdl-30467381

RESUMEN

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.

Asunto(s)

Neoplasias Óseas/secundario; Antígeno CD24/genética; Mutación; Células Madre Neoplásicas/patología; Neoplasias de la Próstata/patología; Proteínas Proto-Oncogénicas p21(ras)/genética; Regulación hacia Arriba/genética; Animales; Carcinogénesis/genética; Movimiento Celular/genética; Proliferación Celular/genética; Forma de la Célula/genética; Técnicas de Silenciamiento del Gen; Humanos; Masculino; Ratones; Invasividad Neoplásica; Neoplasias de la Próstata/genética; Transducción de Señal/genética; Proteína p53 Supresora de Tumor/deficiencia

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Células Madre Neoplásicas / Neoplasias Óseas / Regulación hacia Arriba / Proteínas Proto-Oncogénicas p21(ras) / Antígeno CD24 / Mutación Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google