Overexpression of Tumor Protein p53-regulated Apoptosis-inducing Protein 1 Regulates Proliferation and Apoptosis of Breast Cancer Cells through the PI3K/Akt Pathway

Liang, Yueyang; Wang, Shushu; Liu, Jia

doi:10.4048/jbc.2019.22.e21

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…p53 has been found to induce cell cycle arrest and apoptosis in breast cancer 19 . Thus, we investigate whether MARK2 suppresses the p53‐mediated cell cycle arrest and cell death process in breast cancer cells.…”

Section: Resultsmentioning

confidence: 97%

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

Ponnusamy

Natarajan

Manoharan

2022

J of Cellular Biochemistry

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The microtubule‐affinity regulating kinases (MARKs) family plays a crucial role in regulating breast cancer development and progression. However, its precise function and the relevant molecular mechanism in breast cancer have not yet been elucidated. In this study, analysis of The Cancer Genome Atlas (TCGA) data revealed that MARK2 expression was markedly upregulated in breast cancer tissues, and high expression of MARK2 was correlated with poor survival. Functional assays showed that MARK2 deletion or inhibition suppressed aerobic glycolysis and cell growth as well as induced cell cycle arrest and apoptosis in breast cancer cells. Mechanistically, MARK2 stimulates mTOR‐mediated hypoxia‐inducible factor 1 alpha (HIF‐1α) transcription activity and represses p53‐transcription activity in breast cancer cells. TCGA data revealed that MARK2 expression was positively correlated with mTOR, Raptor, S6K1, glucose transporter 1, lactate dehydrogenase, HIF‐1α, and 4E‐BP1 expression, whereas negatively correlated with p53, p21, and Bax in breast cancer tissue. Conclusively, our study demonstrated that MARK2 promotes breast cancer aerobic glycolysis and cell proliferation, and inhibits apoptosis, in part, through regulating mTOR/HIF‐1α and p53 signaling pathways. Overall, these findings point to the potential of targeting MARK2 for breast cancer treatment.

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Section: Resultsmentioning

confidence: 97%

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

Ponnusamy

Natarajan

Manoharan

2022

J of Cellular Biochemistry

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“…Based on a previous report, ANXA2 knockdown increased the tumour suppressor protein (p53) activity and downstream gene expression, as well as the p53 translocation from the cytoplasm to the nucleus [ 36 ]. p53 protein is the major tumour suppressor and plays an important role in tumour suppression by preventing the division and development of cells with damaged DNA [ 37 , 38 ]. Our findings show that ANXA2 was suppressed in the 9-methoxycanthine-6-one-treated A2780 ovarian cancer cell line.…”

Section: Discussionmentioning

confidence: 99%

The In Vitro Anti-Cancer Activities and Mechanisms of Action of 9-Methoxycanthin-6-one from Eurycoma longifolia in Selected Cancer Cell Lines

et al. 2022

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An alkaloid compound from the hairy root culture of Eurycoma longifolia has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC50 values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro.

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“…Activation of PI3K/Akt promotes the formation and progression of breast cancers [ 17 ]. Inhibition of PI3K/Akt, on the contrary, can trigger the apoptosis of tumor cells [ 38 , 39 ]. Previous studies have shown that overexpression of MUC1 leads to the upregulation of signaling molecules involved in PI3K/Akt/mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor

Zhao

Lin

et al. 2020

Animals

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Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.

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Overexpression of Tumor Protein p53-regulated Apoptosis-inducing Protein 1 Regulates Proliferation and Apoptosis of Breast Cancer Cells through the PI3K/Akt Pathway

Cited by 14 publications

References 28 publications

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

The In Vitro Anti-Cancer Activities and Mechanisms of Action of 9-Methoxycanthin-6-one from Eurycoma longifolia in Selected Cancer Cell Lines

Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor

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