Met Signaling Cascade Is Amplified by the Recruitment of Phosphorylated Met to Lipid Rafts via CD24 and Leads to Drug Resistance in Endometrial Cancer Cell Lines

Endometrial cancer is the most prevalent gynecologic cancer in the Western world, and the number of advanced chemotherapy-resistant cancers is increasing with the absolute increase in patients. The development of resistance to chemotherapeutic drugs by cancer cells represents a major challenge in the clinical cure of advanced and metastatic cancers. CD24 has been reported to be a marker for a poor prognosis in several tumors, and we herein examined the functions of CD24 in human endometrioid adenocarcinoma cell lines and evaluated how it contributes to cancer drug resistance. We demonstrated that CD24 was responsible for the recruitment of phosphorylated Met to the lipid raft domain of the cell membrane, resulting in amplification of the Met signaling cascade, ultimately leading endometrial cancer cells to express higher levels of ATP-binding cassette (ABC) transporters. Our findings suggest that CD24-mediated amplification of the Met cascade may contribute to the drug resistance of endometrial cancer. (C) 2015 AACR.