ZFIN ID: ZDB-PUB-170411-3
CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer
Zoni, E., Chen, L., Karkampouna, S., Granchi, Z., Verhoef, E.I., La Manna, F., Kelber, J., Pelger, R.C., Henry, M.D., Snaar-Jagalska, E., van Leenders, G.J., Beimers, L., Kloen, P., Gray, P.C., van der Pluijm, G., Kruithof-de Julio, M.
Date: 2017
Source: Oncogene   36(33): 4739-4749 (Journal)
Registered Authors: Snaar-Jagalska, Ewa B.
Keywords: none
MeSH Terms:
  • Animals
  • Bone Neoplasms/metabolism
  • Bone Neoplasms/secondary*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • GPI-Linked Proteins/genetics
  • GPI-Linked Proteins/metabolism*
  • Gene Knockdown Techniques
  • Heat-Shock Proteins/genetics
  • Heat-Shock Proteins/metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism*
  • Neoplasm Transplantation
  • Prostatic Neoplasms/genetics
  • Prostatic Neoplasms/pathology*
PubMed: 28394345 Full text @ Oncogene
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 ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. 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 ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh 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.