Journal
MOLECULAR CANCER RESEARCH
Volume 12, Issue 10, Pages 1449-1459Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-13-0587
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Funding
- Ministry of Education, Culture, Science and Technology of Japan
- Ministry of Health, Labor and Welfare of Japan
- Cancer Center Research and Development Fund [23-A-9, 23-B-24]
- Grants-in-Aid for Scientific Research [26290043, 24501327] Funding Source: KAKEN
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Involvement of Ras in cancer initiation is known, but recent evidence indicates a role in cancer progression, including metastasis and invasion; however, the mechanism is still unknown. In this study, it was determined that human lung cancer cells with Ras mutations, among other popular mutations, showed significantly higher expression of CUB domain-containing protein 1 (CDCP1) than those without. Furthermore, activated Ras clearly induced CDCP1, whereas CDCP1 knockdown or inhibition of CDCP1 phosphorylation by Src-directed therapy abrogated anoikis resistance, migration, and invasion induced by activated-Ras. Activation of MMP2 and secretion of MMP9, in a model of Ras-induced invasion, was found to be regulated through induction of phosphorylated CDCP1. Thus, CDCP1 is required for the functional link between Ras and Src signaling during the multistage development of human malignant tumors, highlighting CDCP1 as a potent target for treatment in the broad spectrum of human cancers associated with these oncogenes. (C)2014 AACR.
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