Study on cancer metastasis marker and therapeutics

Cancer is the leading cause of death in Taiwan, and cancer metastasis remains the etiology for 90% of human cancer deaths. Prohibitin (PHB) is indispensable for Ras-induced Raf-1 activation, cell migration and growth; however, the exact role of PHB in the molecular pathogenesis of cancer metastasis remains largely unexamined. In this year, we found a positive correlation between plasma membrane-associated PHB and the clinical stages of cancer. We have also demonstrated that PHB phosphorylated at threonine 258 residue in the raft domain of plasma membrane is required in the Ras-driven activation of PI3K/Akt and Raf-1/ERK-signaling cascades and results in the promotion of cancer metastasis both in vitro and in vivo (Chiu, C. F. et al., Oncogene, 2012). Therefore, phospho-PHB could serve as a therapeutic target for cancer metastasis and inhibition of phospho-PHB could be used to select the novel drugs for suppression of cancer metastasis. We have also found that recombinant protein rVP1 developed in our laboratory inhibits phospho-PHB to suppress tumor growth and cancer metastasis, and prolongs survival of tumor-bearing mice in an orthotopic cervical cancer mice mode (Chiu, C. F. et al., Cancer Letters, 2012). Preliminary acute toxicity test in mice showed that rVP1 did not elicit side effects. Our results suggest that recombinant protein rVP1 is a potential anti-cancer metastatic drug.