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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.