title: Semaphorin-3F suppresses the stemness of colorectal cancer cells by inactivating Rac1.
abstract: Tumor cell stemness has been recognized as a key contributor to tumor initiation, progression and recurrence. Our previous studies have found that semaphorin-3F (SEMA3F), an axon guidance molecule in the development of central nervous system, inhibited the growth and metastasis of colorectal cancer (CRC). However, a possible role for SEMA3F in regulating cancer cell stemness remains unknown. Here, we report a novel mechanism of the acquirement of stemness of CRC cells regulated by SEMA3F. Knockdown of SEMA3F significantly promoted the self-renewal and tumorigenicity of CRC cells, and increased the expression of stemness-associated genes, while overexpressing SEMA3F reduced the stemness of CRC cells. Mechanistically, GTP-Rac1 was involved in SEMA3F mediated regulation of CRC cell stemness by targeting the Wnt/β-catenin pathway. Clinically, GTP-Rac1 expression was inversely correlated with SEMA3F levels in CRC samples and patients with SEMA3F(low)/GTP-Rac1(high) CRC showed poorer prognosis. Our findings demonstrate the ability of SEMA3F to inhibit the stemness of human CRC cells by suppressing Rac1 activation, which suggests a novel therapeutic approach for CRC.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Rao
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhi-Hang
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Sen-Lin
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Ping
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China. Electronic address: hotbayer@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China. Electronic address: bianxiuwu@263.net.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C107953:RAC1 protein, human; C491230:SEMA3F protein, human; D020830:rac1 GTP-Binding Protein
keywords: Cancer stem cells; Colorectal cancer; GTP-Rac1; Semaphorin-3F