Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer

Yang Cao, Xiyong Liu, Wei Lu, Yuanyuan Chen, Xiangsong Wu, Maolan Li, Xu an Wang, Fei Zhang, Lin Jiang, Yijian Zhang, Yunping Hu, Shanshan Xiang, Yijun Shu, Runfa Bao, Huaifeng Li, Wenguang Wu, Hao Weng, Yun Yen, Yingbin Liu

研究成果: 雜誌貢獻文章

33 引文 (Scopus)

摘要

Fibronectin (FN), a heterodimeric glycoprotein overexpressed in several types of tumors, has been implicated in cancer progression via the activation of integrin-mediated pro-oncogenic pathways. The FN level in human bile fluid is dramatically increased in malignant biliary diseases; however, FN expression and its biological functions in gallbladder cancer (GBC) remain unknown. In this study, we found that FN was overexpressed in GBC tissues and was associated with a worse prognosis in GBC patients. In vitro experimental studies indicated that exogenous FN significantly enhanced cell proliferation, invasion and active MMP-9 secretion in human GBC cell lines (GBC-SD and NOZ). Moreover, the key kinases of the mTOR signaling pathway, including FAK, Akt, mTOR and 4E-BP1, were markedly activated in a time-dependent manner in FN-treated GBC-SD and NOZ cells. The IHC statistical analyses validated that FN expression was positively correlated with the phosphorylation levels of the 4E-BP1 protein in GBC tissues. Furthermore, rapamycin, a specific inhibitor of mTOR, almost completely blocked FN-induced phosphorylation of 4E-BP1 and also partially abrogated the stimulatory effects of FN on GBC cell proliferation and invasion. In vivo, FN treatment significantly promoted the proliferation and metastasis of GBC cells and markedly activated Akt/mTOR/4E-BP1 signaling cascade. These findings demonstrate that FN may play a critical role in the modulation of cell proliferation and invasion via mTOR signaling pathway activation during GBC progression.
原文英語
頁(從 - 到)141-150
頁數10
期刊Cancer Letters
360
發行號2
DOIs
出版狀態已發佈 - 五月 1 2015
對外發佈Yes

指紋

Gallbladder Neoplasms
Fibronectins
Cell Proliferation
Phosphorylation
Sirolimus
Matrix Metalloproteinases
Bile
Integrins
Neoplasms
Glycoproteins
Phosphotransferases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

引用此文

Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer. / Cao, Yang; Liu, Xiyong; Lu, Wei; Chen, Yuanyuan; Wu, Xiangsong; Li, Maolan; Wang, Xu an; Zhang, Fei; Jiang, Lin; Zhang, Yijian; Hu, Yunping; Xiang, Shanshan; Shu, Yijun; Bao, Runfa; Li, Huaifeng; Wu, Wenguang; Weng, Hao; Yen, Yun; Liu, Yingbin.

於: Cancer Letters, 卷 360, 編號 2, 01.05.2015, p. 141-150.

研究成果: 雜誌貢獻文章

Cao, Y, Liu, X, Lu, W, Chen, Y, Wu, X, Li, M, Wang, XA, Zhang, F, Jiang, L, Zhang, Y, Hu, Y, Xiang, S, Shu, Y, Bao, R, Li, H, Wu, W, Weng, H, Yen, Y & Liu, Y 2015, 'Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer', Cancer Letters, 卷 360, 編號 2, 頁 141-150. https://doi.org/10.1016/j.canlet.2015.01.041
Cao, Yang ; Liu, Xiyong ; Lu, Wei ; Chen, Yuanyuan ; Wu, Xiangsong ; Li, Maolan ; Wang, Xu an ; Zhang, Fei ; Jiang, Lin ; Zhang, Yijian ; Hu, Yunping ; Xiang, Shanshan ; Shu, Yijun ; Bao, Runfa ; Li, Huaifeng ; Wu, Wenguang ; Weng, Hao ; Yen, Yun ; Liu, Yingbin. / Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer. 於: Cancer Letters. 2015 ; 卷 360, 編號 2. 頁 141-150.
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abstract = "Fibronectin (FN), a heterodimeric glycoprotein overexpressed in several types of tumors, has been implicated in cancer progression via the activation of integrin-mediated pro-oncogenic pathways. The FN level in human bile fluid is dramatically increased in malignant biliary diseases; however, FN expression and its biological functions in gallbladder cancer (GBC) remain unknown. In this study, we found that FN was overexpressed in GBC tissues and was associated with a worse prognosis in GBC patients. In vitro experimental studies indicated that exogenous FN significantly enhanced cell proliferation, invasion and active MMP-9 secretion in human GBC cell lines (GBC-SD and NOZ). Moreover, the key kinases of the mTOR signaling pathway, including FAK, Akt, mTOR and 4E-BP1, were markedly activated in a time-dependent manner in FN-treated GBC-SD and NOZ cells. The IHC statistical analyses validated that FN expression was positively correlated with the phosphorylation levels of the 4E-BP1 protein in GBC tissues. Furthermore, rapamycin, a specific inhibitor of mTOR, almost completely blocked FN-induced phosphorylation of 4E-BP1 and also partially abrogated the stimulatory effects of FN on GBC cell proliferation and invasion. In vivo, FN treatment significantly promoted the proliferation and metastasis of GBC cells and markedly activated Akt/mTOR/4E-BP1 signaling cascade. These findings demonstrate that FN may play a critical role in the modulation of cell proliferation and invasion via mTOR signaling pathway activation during GBC progression.",
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T1 - Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer

AU - Cao, Yang

AU - Liu, Xiyong

AU - Lu, Wei

AU - Chen, Yuanyuan

AU - Wu, Xiangsong

AU - Li, Maolan

AU - Wang, Xu an

AU - Zhang, Fei

AU - Jiang, Lin

AU - Zhang, Yijian

AU - Hu, Yunping

AU - Xiang, Shanshan

AU - Shu, Yijun

AU - Bao, Runfa

AU - Li, Huaifeng

AU - Wu, Wenguang

AU - Weng, Hao

AU - Yen, Yun

AU - Liu, Yingbin

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Fibronectin (FN), a heterodimeric glycoprotein overexpressed in several types of tumors, has been implicated in cancer progression via the activation of integrin-mediated pro-oncogenic pathways. The FN level in human bile fluid is dramatically increased in malignant biliary diseases; however, FN expression and its biological functions in gallbladder cancer (GBC) remain unknown. In this study, we found that FN was overexpressed in GBC tissues and was associated with a worse prognosis in GBC patients. In vitro experimental studies indicated that exogenous FN significantly enhanced cell proliferation, invasion and active MMP-9 secretion in human GBC cell lines (GBC-SD and NOZ). Moreover, the key kinases of the mTOR signaling pathway, including FAK, Akt, mTOR and 4E-BP1, were markedly activated in a time-dependent manner in FN-treated GBC-SD and NOZ cells. The IHC statistical analyses validated that FN expression was positively correlated with the phosphorylation levels of the 4E-BP1 protein in GBC tissues. Furthermore, rapamycin, a specific inhibitor of mTOR, almost completely blocked FN-induced phosphorylation of 4E-BP1 and also partially abrogated the stimulatory effects of FN on GBC cell proliferation and invasion. In vivo, FN treatment significantly promoted the proliferation and metastasis of GBC cells and markedly activated Akt/mTOR/4E-BP1 signaling cascade. These findings demonstrate that FN may play a critical role in the modulation of cell proliferation and invasion via mTOR signaling pathway activation during GBC progression.

AB - Fibronectin (FN), a heterodimeric glycoprotein overexpressed in several types of tumors, has been implicated in cancer progression via the activation of integrin-mediated pro-oncogenic pathways. The FN level in human bile fluid is dramatically increased in malignant biliary diseases; however, FN expression and its biological functions in gallbladder cancer (GBC) remain unknown. In this study, we found that FN was overexpressed in GBC tissues and was associated with a worse prognosis in GBC patients. In vitro experimental studies indicated that exogenous FN significantly enhanced cell proliferation, invasion and active MMP-9 secretion in human GBC cell lines (GBC-SD and NOZ). Moreover, the key kinases of the mTOR signaling pathway, including FAK, Akt, mTOR and 4E-BP1, were markedly activated in a time-dependent manner in FN-treated GBC-SD and NOZ cells. The IHC statistical analyses validated that FN expression was positively correlated with the phosphorylation levels of the 4E-BP1 protein in GBC tissues. Furthermore, rapamycin, a specific inhibitor of mTOR, almost completely blocked FN-induced phosphorylation of 4E-BP1 and also partially abrogated the stimulatory effects of FN on GBC cell proliferation and invasion. In vivo, FN treatment significantly promoted the proliferation and metastasis of GBC cells and markedly activated Akt/mTOR/4E-BP1 signaling cascade. These findings demonstrate that FN may play a critical role in the modulation of cell proliferation and invasion via mTOR signaling pathway activation during GBC progression.

KW - Fibronectin

KW - Gallbladder cancer

KW - Invasion

KW - MTOR

KW - Proliferation

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JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

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