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Down-regulation of KLF5 in cancer-associated fibroblasts inhibit gastric cancer cells progression by CCL5/CCR5 axis
Authors:Tingsong Yang  Min Chen  Xiaohu Yang  Xiaobing Zhang  Zhou Zhang  Yingying Sun
Institution:1. Department of General Surgery, Shanghai Tenth Peoples' Hospital affiliated Tongji University, No. 301, Middle Yanchang Road, Shanghai, China;2. Department of Pathology, Dahua Hospital, No. 901, Old Humin Road, Xuhui District, Shanghai, China;3. Department of Anesthesiology, Shanghai East Hospital Affiliated Tongji University, No. 150, JiMo Road, Shanghai, China
Abstract:It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblasts compared with normal mucosal fibroblasts. Moreover, KLF5 expression in tumor stroma was closely associated with clinicopathological features such as tumor size, invasion depth, cell grade and lymph node metastasis, as well as poor prognosis in patients with gastric cancer. In addition, we further demonstrated that KLF5-regulating CAFs affect gastric cancer cells progression by CCL5 secretion and activation of CCR5. Taken together, we concluded that KLF5 expression in gastric cancer-associated fibroblasts contribute to poor survival and promote cancer cells progression by activation of CCL5/CCR5 axis, which suggesting that KLF5 in CAFs might be considered as a promising target for the treatment of gastric cancer.
Keywords:Cancer-associated fibroblasts  Gastric cancer  KLF5  CCL5  CCR5
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