title: MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation.
abstract: Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH(high)) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH(high) population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan. Electronic address: hirohash@sapmed.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Takaya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan. Electronic address: torigoe@sapmed.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005833:Genital Neoplasms, Female / Q000235:genetics* / Q000473:pathology; D005836:Genitalia, Female / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D048292:Mitogen-Activated Protein Kinase 13 / Q000032:analysis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D048292:Mitogen-Activated Protein Kinase 13
keywords: Cancer stem cell; Gynecologic cancer; MAPK13; Tumor-initiation