title: 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.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan. bigfootman@mac.com.
authors.forename: Yoshihiro Joshua
authors.initials: YJ
authors.lastname: Ono
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanabe
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Terai
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Ohmichi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051927:CD24 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin