A novel PI3K/AKT signaling axis mediates Nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growth

Zhang, Yijian; Liu, Shibo; Wang, Lei; Wu, Yaoshi; Hao, Jiaqi; Wang, Zheng; Lü, Wei; Wang, Xuan; Zhang, Fei; Yang, Cao; Liang, Haibin; Li, Huaifeng; Ye, Yuanyuan; Ma, Qiang; Zhao, Shuai; Shu, Yijun; Bao, Runfa; Jiang, Lin; Hu, Yunping; Zhou, Jian; Chen, Lei; Liu, Yingbin

doi:10.1016/j.canlet.2016.02.049

Cited by 74 publications

(83 citation statements)

References 36 publications

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“…As an important apoptotic signaling pathway, PI3K/Akt has been detected to play significant roles in inhibiting glioma cell apoptosis and promoting cell proliferation . A previous study also revealed that the suppression of PI3K/Akt signaling pathway could impair the tumor cell proliferation and survival . The inactivation of PI3K/Akt signaling pathway was as well proved to delay glioma cell proliferation and tumor growth through the Wnt/β‐catenin pathway .…”

Section: Discussionmentioning

confidence: 98%

Retracted: MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway

Hong

Wen

et al. 2018

IUBMB Life

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Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia‐1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor‐adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2‐associated X (Bax), B lymphoma Mo‐MLV insertion region 1 homolog (Bmi‐1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit‐8 assay was applied to detect cell proliferation, β‐galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi‐1, and Bcl‐2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi‐1, and Bcl‐2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81–92, 2019

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Section: Discussionmentioning

confidence: 98%

Retracted: MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway

Hong

Wen

et al. 2018

IUBMB Life

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“…Strikingly, recent data demonstrate that metastasis occurs early in the development of GBC, even prior to the formation of the primary tumor [8]. While one goal of cytotoxic therapies is to minimize metastatic tumor growth, therapies specifically designed to inhibit tumor migration and invasion, which underly metastasis, are not currently available [9].…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Zhang

et al. 2017

J Exp Clin Cancer Res

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BackgroundPatients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.MethodsLevels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.ResultsTCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.ConclusionsThese findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0531-3) contains supplementary material, which is available to authorized users.

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“…DHM inhibition of GSK-3β activity may contribute to DA neuronal protection The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt/ PKB) signaling pathway plays a key role in cell survival, proliferation and differentiation [29][30][31] . Akt is a direct downstream effector of the PI3K pathway and is activated by phosphorylation at Ser473.…”

Section: Dhm Protects Da Neurons From Mpp + Toxicity and Inhibits Thementioning

confidence: 99%

Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity

et al. 2016

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A novel PI3K/AKT signaling axis mediates Nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growth

Cited by 74 publications

References 36 publications

Retracted: MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway

Retracted: MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway

Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity

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