Regulation of angiogenesis and tumor growth by p110 Alpha and AKT1 via VEGF expression

Xia, Chang; Qiao, Meng; Cao, Ziping; Shi, Xianglin; Jiang, Bing-Hua

doi:10.1002/jcp.20707

Cited by 70 publications

(64 citation statements)

References 63 publications

(56 reference statements)

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“…Akt3 has been the least studied of the isoforms, but investigations show that Akt3 may have a possible role in brain development (35). The growth regulation properties of Akt1 have made it a major target in cancer studies (32,36,37), especially PTEN-mediated inhibition of Akt1 in tumor development (38). The selectively of GR␤ for Akt1 indicates a potential capacity of this nuclear receptor in growth pathways.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Stechschulte

Wuescher

Marino

et al. 2014

Journal of Biological Chemistry

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Background:The glucocorticoid receptor ␤ (GR␤) is a positive regulator of growth. Results: GR␤ suppression of PTEN resulted in enhanced phosphorylation of Akt and growth. Conclusion: GR␤ enhances insulin-induced proliferation by suppressing PTEN and activating Akt1. Significance: GR␤ suppression of PTEN indicates that it has an important role in growth factor signaling and potentially cancer.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Stechschulte

Wuescher

Marino

et al. 2014

Journal of Biological Chemistry

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“…Relatively, the same phenomenon has not found among cancer patients that have other distant organ metastasis like lung and liver. The secretion of VEGF could be mediated by hypoxia inducible factor 1‐alpha (HIF‐1α), and that plays a critical role in neovascularization 46. As known, once Akt was phosphorylated, several downstream pathways that strongly related to tumor metastasis would be activated.…”

Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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“…Vascular endothelial growth factor (VEGF) is identified as a major mediator of angiogenesis. It can induce endothelial cells to undergo angiogenesis, which facilitates the development of some diseases [3,4], and also plays an important role in the regulation of tumor angiogenesis [5,6].…”

Section: Introductionmentioning

confidence: 99%

Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

et al. 2008

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There is evidence to suggest that follicle-stimulating hormone (FSH) can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor (VEGF) expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose-and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxiainducible factor-1 (HIF-1α). Knockdown of survivin or HIF-1α suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K)/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT (pAKT) protein staining than did benign ovarian cystadenoma samples (p < 0.01). The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursuing effective treatment against this disease.

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Regulation of angiogenesis and tumor growth by p110 Alpha and AKT1 via VEGF expression

Cited by 70 publications

References 63 publications

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Emerging findings into molecular mechanism of brain metastasis

Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

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