title: Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling.
abstract: The translationally controlled tumor protein (TCTP) can be secreted independently of the endoplasmic reticulum/Golgi pathway and has extrinsic activities when it is characterized as the histamine releasing factor (HRF). Despite its important role in allergies and inflammation, little is known about how extracellular TCTP affects cancer progression. In this study, we found that TCTP was overexpressed in the interstitial tissue of colorectal cancer (CRC) and its expression correlated with poor survival, high pathological grades and metastatic TNM stage in CRC patients. TCTP expression was greater in metastatic liver tissue than in primary tumors and was increased in highly invasive CRC cells. We demonstrated that the expression of TCTP was regulated by HIF-1α and its release was increased in response to low serum and hypoxic stress. Recombinant human TCTP (rhTCTP) promoted the migration and invasiveness of CRC cells in vitro and contributed to distant liver metastasis in vivo. Furthermore, rhTCTP activated Cdc42, phosphorylated JNK (p-JNK), increasing the translocation of p-JNK from the cytoplasm to the nucleus, as well as the secretion of MMP9. In addition, the expression of TCTP positively correlated with that of Cdc42 and p-JNK in clinical CRC samples. The silencing of Cdc42, JNK and MMP9 significantly inhibited the Matrigel invasion of rhTCTP-enhanced CRC cells. Collectively, these results identify a new role for extracellular TCTP as a promoter of CRC progression and liver metastases via Cdc42/JNK/MMP9 activation.
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.|RayBiotech, Inc., Guangzhou 510600, China.|RayBiotech, Inc., Norcross, GA 30092, USA.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Anorectal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Tiancai
authors.initials: T
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Suihai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, 303 Hospital of People's Liberation Army, Nanning 530021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Laboratory Medicine, Guangzhou General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong 510010, China.
authors.forename: Linhai
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Division of Clinical Immunology Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Daming
authors.initials: D
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Yingsong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020868:Gene Silencing; D006801:Humans; D000860:Hypoxia; D007249:Inflammation; D008099:Liver / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D000090324:Tumor Protein, Translationally-Controlled 1; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D048670:MAP Kinase Kinase 4; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; extracellular TCTP; metastasis; p-JNK