title: MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma.
abstract: Matrix metalloproteinases play an essential role in the progression of esophageal squamous cell carcinoma (ESCC). Here, we show that MMP1 expression was markedly increased in a majority of ESCC compared with nontumorous tissue. High expressions of MMP1 were closely associated with lymph node metastasis, microvessel density and advanced TNM stage. Kaplan-Meier and multivariate analyses indicated MMP1 as an independent factor for overall survival in two independent cohorts of 613 patients with ESCC. In vitro studies demonstrated that MMP1 overexpression resulted in enhanced cell viability, abilities of colony formation and cell migration. The knockdown of MMP1 in ESCC cells resulted in the opposite phenomenon. Consistently, in vivo data showed that ectopic expression of MMP1 promoted tumor growth and metastasis. Further study revealed that MMP1 facilitated ESCC through the activation of the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway by LY294002 significantly attenuated MMP1-mediated cell proliferation and migration. Taken together, our data suggest that MMP1 functions as an oncogene and serves as a prognostic biomarker and a potential therapeutic target in ESCC.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Kong-Jia
authors.initials: KJ
authors.lastname: Luo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Xie
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Fu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: yanghong@sysucc.org.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C569392:MIRN202 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Esophageal squamous carcinoma; MMP1; Metastasis; PI3K/AKT