A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition

Xu, Wenting; Yang, Zhen; Lü, Nonghua

doi:10.1080/19336918.2015.1016686

Cited by 468 publications

(348 citation statements)

References 92 publications

(86 reference statements)

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“…PI3K and AKT have been reported as upstream factors regulating cell cycle progression and EMT [19, 20]. We also examined the effect of ZNF703 on the PI3K/Akt signalling pathway and found that the loss of ZNF703 reduced the expression of phosphorylated PI3K (Tyr458), Akt (Ser473) and GSK-3 (Ser9), whereas the expression of PI3K, Akt and GSK-3β remained unchanged (Fig.…”

Section: Resultsmentioning

confidence: 99%

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Wang

Deng

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Zinc finger protein 703 (ZNF703), initially identified as a novel oncogene in human breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. It is recognized that the overexpression of ZNF703 is associated with various types of human cancers, but the role and molecular mechanism of ZNF703 in oral squamous cell carcinoma (OSCC) are unknown. Methods: ZNF703 expression levels were examined in OSCC tissues and non-cancerous tissues by qRT-PCR and immunohistochemistry (IHC). The molecular mechanisms of ZNF703 and its effects on cell growth and metastasis were explored in vitro and in vivo using the CCK8 assay, colony formation assay, cell cycle analysis, migration and invasion assays, wound-healing assay, western blotting and xenograft experiments in nude mice. Results: In this study, ZNF703 was found to be upregulated in OSCC tissues compared to that in normal tissues at both mRNA and protein levels, and its expression level was closely correlated with the overall survival of patients with OSCC. Silencing of the ZNF703 gene in OSCC cells significantly inhibited cell growth and metastasis in vitro and in vivo. Conversely, the overexpression of ZNF703 in OSCC cells promoted cancer growth and metastasis in vitro. Mechanistically, ZNF703 activated the PI3K/AKT/GSK-3β signalling pathway and its downstream effectors, thus regulating the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, the promotive effects of ZNF703 on cellular proliferation and metastasis could be rescued by LY294002 (a PI3K-specific inhibitor) and MK2206 (an Akt-specific inhibitor). Conclusion: The results show that ZNF703 promotes cell growth and metastasis through PI3K/Akt/GSK-3β signalling in OSCC and that it may be a promising target in the treatment of patients with OSCC.

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Section: Resultsmentioning

confidence: 99%

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Wang

Deng

Zhang

et al. 2017

Cell Physiol Biochem

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“…Subsequent to these morphological and biochemical changes, cells acquire the motile and invasive phenotype characteristics of mesenchymal cells [8]. These cells express the mesenchymal markers, such as vimentin, fibronectin, N-cadherin, twist and snail [9]. However, the molecular mechanisms that govern the overarching framework of EMT plasticity have yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial–mesenchymal transition in triple‐negative breast cancer

Zhao

Liu

et al. 2016

J Cellular Molecular Medi

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Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up-regulated in TNBC and associated with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. Moreover, silencing of Prrx1b prevented Wnt/b-catenin signaling pathway and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a new therapeutic target for interventions against TNBC invasion and metastasis.

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“…Recently, increasing evidence has indicated that the activation of the PI3K/Akt signaling pathway may play an important role in promoting invasion and metastasis in resistant cells (15). It is, therefore, of significant interest to examine whether sorafenib-induced EMT is attributable to the activation of the PI3K/Akt cascade.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

Zhang

Wang

et al. 2018

Oncol Lett

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Abstract. Long-term sorafenib treatment triggers resistance to chemotherapy in patients with hepatocellular carcinoma (HCC). In order to investigate the mechanisms of sorafenib resistance in HCC, the aim of the present study was to develop a resistant human liver cell line via long-term exposure to sorafenib. The cytotoxicity cell counting kit-8 assay was used to evaluate drug sensitivity. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine the molecular mechanisms underpinning sorafenib resistance. Migratory and invasive properties in resistant cells were assessed using Transwell assays. The results from the present study revealed that resistant cells became insensitive to sorafenib treatment and exhibited increased migratory and invasive capacities. Activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway and epithelial-mesenchymal transition was characteristic of resistant cells. The use of LY294002, a PI3K inhibitor, was able to suppress the activation of Akt and extracellular signal-regulated kinase 1/2, attenuated the migratory and invasive capacities of resistant cells. Data from the present study indicates that inhibition of the PI3K signaling pathway with LY294002 exerts suppressive effects on sorafenib resistance and provides an attractive novel therapeutic regime in patients with advanced HCC.

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A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition

Cited by 468 publications

References 92 publications

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

RETRACTED: Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial–mesenchymal transition in triple‐negative breast cancer

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

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