title: Transcriptional activation of FN1 and IL11 by HMGA2 promotes the malignant behavior of colorectal cancer.
abstract: Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, and metastasis is the principle reason for its poor prognosis. Overexpression of high-mobility gene group A2 (HMGA2) contributes to the aggressiveness of CRC. However, the underlying molecular mechanism of its overexpression is still elusive. In this study, we showed that ectopic expression of HMGA2 significantly enhanced cell migration and invasion in vitro and promoted tumor growth and distant metastasis in vivo In contrast, the silencing of HMGA2 produced the opposite effects in vitro and in vivo Chromatin immunoprecipitation-PCR and luciferase assays revealed that HMGA2 bound directly to the promoters of FN1 and IL11 and significantly induced their transcriptional activities. Moreover, as the direct downstream target of HMGA2, IL11 modulated cell migration and invasion through a pSTAT3-dependent signaling pathway. Furthermore, a strong positive correlation between HMGA2 and IL11 expression was identified in 122 CRC tissues. High IL11 expression was associated with poor differentiation, a large tumor size, lymph node metastasis and low overall survival in CRC patients. Collectively, our data reveal novel insights into the molecular mechanisms underlying HMGA2-mediated CRC metastasis and highlight the possibility of targeting HMGA2 and IL11 for treating CRC patients with metastasis.
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Sana
authors.initials: S
authors.lastname: Sahengbieke
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China lmp@zju.edu.cn.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: C067625:FN1 protein, human; D005353:Fibronectins; D025743:HMGA2 Protein; C508611:IL11 protein, human; D017370:Interleukin-11; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human