New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer

Yang, Sherry X.; Polley, Eric C.; Lipkowitz, Stanley

doi:10.1016/j.ctrv.2016.03.004

Cited by 190 publications

(163 citation statements)

References 98 publications

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“…The PI3K/AKT/GSK-3β pathway is a classical signalling pathway in tumourigenesis [36, 37], and its activation upregulates the expression of Snail and Slug, thereby promoting EMT [20, 38, 39] and inducing the transition from G1 to S phase [40, 41]. In this study , we found that the loss of ZNF703 expression decreased the expression of p-PI3K, p-Akt, and p-GSK-3β.…”

Section: Discussionmentioning

confidence: 80%

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: Discussionmentioning

confidence: 80%

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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“…Previous studies have indicated that the Akt signaling pathway is a key factor in the viability and migration of a number of types of tumor including colorectal (32), and prostate cancer (33), and glioblastoma (34) and osteosarcoma (35). Additionally, the Akt signaling pathway is an important regulator of breast cancer (36)(37)(38). Apoptosis disorders are an additional cause for the occurrence of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Shen¹,

Zeng²,

Pan³

et al. 2018

Oncol Lett

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Abstract. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in a number of types of malignant epithelial cancer. However, the mode of action of TMP on breast cancer cells remains unknown. The aim of the present study was to investigate the regulatory effect of TMP on breast cancer cells and its underlying molecular mechanism of action. Different concentrations of TMP were used to treat breast cancer cells, and subsequently, the effects on the viability, apoptosis, and migration and invasion abilities were determined. In addition, the expression and activity levels of the protein kinase B (Akt) signaling pathway and caspase-3 were explored via reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study revealed that TMP significantly inhibited the viability, migration and invasion rates, and increased the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The minimum effective dose was ~1,600 µM. Additional mechanistic studies demonstrated that 1,600 and 3,200 µM TMP significantly decreased the gene expression and activity of Akt and increased the activity of caspase-3. This mechanism may be responsible for the inhibition of viability, migration and invasion, and activation of apoptosis in breast cancer cells. The results of the present study suggested that TMP may be used in chemotherapy against breast cancer.

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“…HER family tyrosine kinase inhibitors in combination therapies) and other parallel nodal pathways (e.g. MAPK) is more effective to inhibit tumor growth and prevent emergence of regulatory feedback loops and development of drug resistance [34-36]. …”

Section: Deregulated Pi3k/akt Activation In Cancermentioning

confidence: 99%

The Hidden Conundrum of Phosphoinositide Signaling in Cancer

et al. 2016

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Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g. mTORC1) dominates the landscape of phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC), and is now an established lipid messenger pivotal for different cellular events in cancer. Here, we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol phosphate (PIP) kinases (PIPKs). We highlighted how PI(4,5)P2 and PIP kinases serve as a proximal node in phosphoinositide signaling axis and how its interaction with cytoskeletal proteins regulates migratory and invasive nexus of metastasizing tumor cells.

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New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer

Cited by 190 publications

References 98 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

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

The Hidden Conundrum of Phosphoinositide Signaling in Cancer

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