title: Gap junction as an intercellular glue: Emerging roles in cancer EMT and metastasis.
abstract: Metastasis is a common phenomenon in the progression and dissemination of cancer. It is estimated that metastasis accounts for 90% cancer-related mortality. Although the formation of tumor metastasis is relatively well understood, the underlying molecular mechanisms responsible for the emergence of aggressive cancer phenotype are still elusive. Figuring out the mechanisms by which cancer cells evade from the tumor is beneficial for obtaining novel and effectively therapeutic approaches. Primary tumors are composed of various subpopulations of cells with heterogeneous metastatic characteristics and the occurrence of metastatic dissemination is mainly dependent upon the interactions between tumor and the surrounding microenvironment. Tumor microenvironment (TME) such as extracellular matrix, macrophages, fibroblasts, stem cells and endothelial cells can orchestrate events critical to tumor evolution toward metastasis. GJ serves as an important communication between tumor cells and stromal cells. Increased GJs coupling blocks metastatic potential in some cancer animal models such as breast cancer and melanoma. Besides, epithelial-to-mesenchymal transition (EMT) is also a crucial step in the metastatic process and there are signs that GJs contribute to cell adhesion and migration (the pathological feature of EMT) in breast cancer. Therefore, we propose that GJ serves as an intercellular glue to suppress EMT and cancer metastasis.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. Electronic address: maoxiaoyuan2011@163.com.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Mao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
authors.forename: Qiu-Qi
authors.initials: QQ
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Gao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. Electronic address: liuzhaoqian63@126.com.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National Centers for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: weilinjin@yahoo.com.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Jin
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D017630:Connexins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D017630:Connexins
keywords: Cancer metastasis; Connexin; Epithelial–mesenchymal transition; Gap junction; Tumor microenvironment