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CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer
- Source :
- Oncogene, 36(33), 4739-4749. Nature Publishing Group, Oncogene, Oncogene, 36(33), 4739-4749. NATURE PUBLISHING GROUP, Oncogene, 36, 4739-4749
- Publication Year :
- 2017
-
Abstract
- CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDH(high) sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDH(low). Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDH(high) sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDH(high) sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Mice, Nude
Bone Neoplasms
Kaplan-Meier Estimate
Biology
Cripto
GPI-Linked Proteins
Molecular oncology
Metastasis
03 medical and health sciences
Prostate cancer
Mice
Growth factor receptor
SDG 3 - Good Health and Well-being
Cell Movement
Cell Line, Tumor
Genetics
medicine
Animals
Humans
Molecular Biology
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Cell Proliferation
Cancer
Bone metastasis
Prostatic Neoplasms
medicine.disease
Neoplasm Proteins
030104 developmental biology
Gene Knockdown Techniques
Immunology
Cancer cell
Cancer research
Intercellular Signaling Peptides and Proteins
Original Article
hormones, hormone substitutes, and hormone antagonists
Neoplasm Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 09509232 and 47394749
- Database :
- OpenAIRE
- Journal :
- Oncogene, 36(33), 4739-4749. Nature Publishing Group, Oncogene, Oncogene, 36(33), 4739-4749. NATURE PUBLISHING GROUP, Oncogene, 36, 4739-4749
- Accession number :
- edsair.doi.dedup.....0f4645ffd2a127d7055b2afd3b45146b