title: MFAP3L activation promotes colorectal cancer cell invasion and metastasis.
abstract: An abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly correlates with distant metastasis in colorectal cancer (CRC), although the mechanism has yet to be explained. In this study, we observed that MFAP3L knock-down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated the cellular location and biochemical functions of MFAP3L and found that this protein was primarily localized in the nucleus of CRC cells and acted as a protein kinase. When EGFR translocated into the nucleus upon stimulation with EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic behavior of CRC cells in vitro and in vivo could be partially explained by activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we experimentally demonstrated for the first time that MFAP3L likely participates in the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that impacts CRC metastasis.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lou
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Hao
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Tian
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China.
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing 100021, China.
authors.forename: Ningzhi
authors.initials: N
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Institute for Cancer Research, 52 Fucheng Road, Haidian District, Beijing 100142, China. Electronic address: yongylu@public.bta.net.cn.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China. Electronic address: siqiliu@big.ac.cn.
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003285:Contractile Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D003285:Contractile Proteins; D034741:RNA, Small Interfering; C094154:MFAP3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
keywords: Colorectal cancer; MFAP3L; Metastasis; Protein kinase