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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Cancer+Res
2015 ; 5
(10
): 3085-97
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Progranulin promotes colorectal cancer proliferation and angiogenesis through
TNFR2/Akt and ERK signaling pathways
#MMPMID26693061
Yang D
; Wang LL
; Dong TT
; Shen YH
; Guo XS
; Liu CY
; Liu J
; Zhang P
; Li J
; Sun YP
Am J Cancer Res
2015[]; 5
(10
): 3085-97
PMID26693061
show ga
Progranulin (PGRN) has been shown to be involved in the process of inflammation,
wound healing, and cartilage development; and its role in the progression of
breast and ovarian cancer is also well established. However, the expression
status of PGRN in colorectal cancers (CRCs) and its molecular mechanisms
responsible for tumorigenesis have not been addressed so far. Herein, we
demonstrated that PGRN was highly expressed and had clinical relevance with CRCs
since its overexpression was associated with advanced stages of CRCs, poorer
patients' prognosis, and increased expression of proliferation and angiogenesis
markers. PGRN up-regulation significantly promoted the expression of Ki67 and
vascular endothelial growth factor A (VEGF-A) as well as the growth rate in CRC
cell lines, while PGRN down-regulation had the opposite effects. Strikingly, PGRN
derived from CRCs could directly induce proliferation, migration, tubule
formation, as well as VEGF-A expression in human umbilical vein endothelial cells
(HUVECs). Furthermore, we provided mechanistic evidences that the regulation of
Ki67 and VEGF-A expression by PGRN was mediated by tumor necrosis factor receptor
2 (TNFR2)/Akt and the ERK signaling pathways in both CRC cells and HUVECs. Taken
together, these findings suggested that PGRN could promote proliferation and
angiogenesis through TNFR2/Akt and ERK signaling pathways in CRCs, providing the
new insight into the mechanism of PGRN in tumor proliferation and angiogenesis.