title: CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of Snail signaling in gastric cancer.
abstract: The chemokine receptor 7 (CCR7) and Snail signaling have been linked to various types of cancers. The associations between these signalings and the epithelial-mesenchymal transition (EMT) are not clear in gastric cancer. Here, the expression of CCR7 and Snail was detected in gastric cancer by immunohistochemistry and Western blot. Meanwhile, gastric cancer cells were subjected to CCL19, si-control, and si-Snail treatment. Cell cycle, migration, and invasion were also analyzed. The expression patterns of CCR7 and Snail were similar in either gastric cancer tissues or cells. The increased expression of CCR7 was closely associated with the increased Snail expression, which both were closely correlated with metastasis, stage and differentiation, and poor prognosis. The increased p-ERK, p-AKT, Snail, and MMP9 expression and the decreased E-cadherin were confirmed in MGC803 cells in a dose-dependent manner in response to CCL19 treatment. However, the blockade of Snail abrogated the up-regulation of MMP9 and down-regulation of E-cadherin. CCR7-induced ERK and PI3K pathway regulated Snail signaling. Besides si-Snail treatment led to MGC803 cell cycle arrest and affected the migration and invasion. In conclusion, our study suggested that CCR7 promotes Snail expression to induce the EMT, resulting in cell cycle progression, migration, and invasion in gastric cancer. CCR7-Snail pathway provided more potential regimens for cancer therapy.
authors.affiliation: The Third Department of Geriatrics, The First Hospital of Shijiazhuang City, 36# Fanxi Road, Shijiazhuang, 050011, Hebei, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunzhe
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000368:Aged; D015153:Blotting, Western; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D054400:Receptors, CCR7 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C515370:CCR7 protein, human; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors