Control of colorectal metastasis formation by K-Ras.
Mutational activation of the K-Ras proto-oncogene is frequently observed during the very early stages of colorectal cancer (CRC) development. The mutant alleles are preserved during the progression from pre-malignant lesions to invasive carcinomas and distant metastases. Activated K-Ras may therefore not only promote tumor initiation, but also tumor progression and metastasis formation. Metastasis formation is a very complex and inefficient process: Tumor cells have to disseminate from the primary tumor, invade the local stroma to gain access to the vasculature (intravasation), survive in the hostile environment of the circulation and the distant microvascular beds, gain access to the distant parenchyma (extravasation) and survive and grow out in this new environment. In this review, we discuss the potential influence of mutant K-Ras on each of these phases. Furthermore, we have evaluated the clinical evidence that suggests a role for K-Ras in the formation of colorectal metastases.
Smakman
Niels
N
Department of Surgery G04-228, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508GA Utrecht, The Netherlands.
Borel Rinkes
Inne H M
IH
Voest
Emile E
EE
Kranenburg
Onno
O
D002403:Cathepsins / Q000235:genetics; D016764:Cell Polarity; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D000090063:Proto-Oncogene Mas
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002403:Cathepsins