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10.1038/oncsis.2017.74

http://scihub22266oqcxt.onion/10.1038/oncsis.2017.74
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suck abstract from ncbi


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pmid28846080
      Oncogenesis 2017 ; 6 (8 ): e375
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  • Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3?/?-catenin signaling pathway #MMPMID28846080
  • Chen Q ; Yang D ; Zong H ; Zhu L ; Wang L ; Wang X ; Zhu X ; Song X ; Wang J
  • Oncogenesis 2017[Aug]; 6 (8 ): e375 PMID28846080 show ga
  • Stromal cell populations in the tumor microenvironment (TME) play a critical role in the oncogenesis and metastasis of renal cell carcinoma. In this study, we found that there are ?-smooth muscle actin positive (?-SMA (+)) cells in the stroma of clear cell renal cell carcinoma (ccRCC) tissues, and their numbers are significantly associated with poor survival in ccRCC patients. Interleukin 6 (IL-6) is a critical diver that induces ?-SMA (+) cells in ccRCC tissues via promotion of epithelial to mesenchymal transition (EMT) and stimulates migration and invasion in ccRCC. Peritumoral CD4+ T cells are the main source of IL-6 in ccRCC tissues. In addition to biochemical factors, mechanical compression within tumors affects tumor cell behavior. Tumors grown in a confined space exhibit intratumoral compressive stress and, with sufficient pressure, stress-stimulated migration of cancer cells. Moreover, a combination of IL-6 secreted by CD4+ T cells and growth-induced solid stress further contributes to the regulation of cancer cell morphogenesis, EMT and acquisition of a stemness phenotype. The effects in the combination group were driven by the Akt/GSK-3?/?-catenin signaling pathway, and deregulation of ?-catenin expression was predictive of poor outcome in ccRCC patients. Notably, the expression of a cancer stem cell marker, CD44, was correlated with T stage, high Fuhrman grade and metastasis in ccRCC. These data provide evidence for new stress-reducing and IL-6 targeting strategies in cancer therapy.
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