title: Identification and functional analysis of variants of a cancer/testis antigen LEMD1 in colorectal cancer stem-like cells.
abstract: Colorectal cancer (CRC) is one of the most common malignancy, and the prognosis is not still satisfactory due to treatment resistance, recurrence and distant metastasis. Cancer stem cells (CSCs)/cancer-initiating cells (CICs) is endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability, and CSCs/CICs are resistant to treatments. Thus, CSCs/CICs are thought to be responsible for recurrence and distant metastasis, and eradication of CSCs/CICs is essential to cure CRCs. However, the molecular mechanisms of CSCs/CICs are remain unknown, and we aimed to elucidate molecular aspects of CR-CSCs/CICs in this study. We screened the transcriptome data of primary human CR-CSCs/CICs that we previously established, and found that LEM domain containing 1 (LEMD1) is preferentially expressed in CR-CSCs/CICs. LEMD1 belongs to cancer-testis (CT) antigen, and has five transcript variants (variant 1 [V1] - variant 5 [V5]). We found that LEMD1 V1, V2 and V3 is expressed in testis and CR-CSCs/CICs, whereas LEMD1 V4 and V5 is ubiquitously expressed. LEMD1 gene knockdown experiments using siRNAs and gene overexpression experiments revealed that LEMD1 has a role in the maintenance of CR-CSCs/CICs. These observations indicate that CR-CSC/CIC-specific LEMD1 variants are reasonable target of CR-CSC/CIC-targeted therapy.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Takeda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 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 Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan; Department of Surgery, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Murai
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 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, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 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, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishidate
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kutomi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, South1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South1 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: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000378:metabolism; D013737:Testis / Q000378:metabolism
chemical_list: C495106:LEMD1 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms
keywords: Cancer stem cell; Cancer/testis antigen; Colorectal cancer; LEMD1; Splicing variant