Opposing roles of the oncogene Akt isoforms in tumour progression: is there a dark side to Akt pathway inhibition?

Veeriah, Selvaraju

doi:10.1007/s12154-012-0076-z

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Recent studies have highlighted the importance of the PI3K/Akt axis in various types of tumor cells. PI3K/Akt signaling is implicated in different processes that are characteristic of cancer including growth signal autonomy, insensitivity to antiproliferation signals, inhibition of apoptosis, angiogenesis, invasion and metastasis [ 48 ]. In the current study, western blot analysis of B16–F10 xenografts showed that the phosphorylation level of PI3K/Akt increased with the dose of roxarsone administered (Fig.…”

Section: Discussionmentioning

confidence: 99%

Roxarsone induces angiogenesis via PI3K/Akt signaling

Wang

Yin

et al. 2016

Cell Biosci

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Background3-Nitro-4-hydroxy phenyl arsenic acid, roxarsone, is widely used as an organic arsenic feed additive for livestock and poultry, which may increase the level of arsenic in the environment and the risk of exposure to arsenic in human. Little information is focused on the angiogenesis roxarsone-induced and its mechanism at present. This paper aims to study the role of PI3K/Akt signaling in roxarsone-induced angiogenesis in rat vascular endothelial cells and a mouse B16–F10 melanoma xenograft model.ResultsThe results showed that treatment with 0.1–10.0 µmol/L roxarsone resulted in an increase in the OD rate in the MTT assay, the number of BrdU-positive cells in the proliferation assay, the migration distance in the scratch test and the number of meshes in tube formation assay. Further, treatment with 1.0 µmol/L roxarsone was associated with significantly higher phosphorylation of PI3K/Akt and expression of VEGF than the control treatment. The PI3K inhibitor was found to significantly combat the effects of 1.0 µmol/L roxarsone. Furthermore, roxarsone treatment was observed to increase the weight and volume of B16–F10 xenografts and VEGF expression and PI3K/Akt phosphorylation in a dose-dependent manner, with the 25 mg/kg dose having significant effects.ConclusionsThese results demonstrate that roxarsone has the ability to promote growth and tube formation in vascular endothelial cells and the growth of mouse B16–F10 xenografts. Further, the findings also indicate that PI3K/Akt signaling plays a regulatory role in roxarsone-induced angiogenesis in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Roxarsone induces angiogenesis via PI3K/Akt signaling

Wang

Yin

et al. 2016

Cell Biosci

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“…Although these AKT family members share a similar domain structure, they have distinct substrates and different physiological behaviors [ 29 ]. These AKT isoforms seem to mediate different functions in cancer pathophysiology; for example, AKT1 appears to promote mammary tumor induction, whereas AKT2 promotes metastasis in previous reports [ 29 , 30 ]. This may explain the difference in the prognostic effects between p-AKT1 and p-AKT2 in ESCC patients in our study.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma

Zhu

Yu²,

et al. 2015

J Exp Clin Cancer Res

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BackgroundThe epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).MethodsExpression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).Resultsp-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.ConclusionActivation of AKT1 was associated with poor prognosis in ESCC.

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“…Interestingly, Akt1 and Akt2 play opposite role on controlling invasion in breast cancer cells, while Akt2 promotes cell invasion, 40,41 Akt1 actually inhibits cell invasion. [42][43][44] To further test which Akt isoform(s) interacts with UCH-L1, we performed His-rhUCH-L1 pulldown assay as described in Fig. 3.…”

Section: Uch-l1 Activates Akt Pathway Through Directly Binding To Akt2mentioning

confidence: 99%

UCH‐L1 promotes invasion of breast cancer cells through activating Akt signaling pathway

Luo

Yang

et al. 2017

J of Cellular Biochemistry

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Opposing roles of the oncogene Akt isoforms in tumour progression: is there a dark side to Akt pathway inhibition?

Cited by 4 publications

References 26 publications

Roxarsone induces angiogenesis via PI3K/Akt signaling

Roxarsone induces angiogenesis via PI3K/Akt signaling

Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma

UCH‐L1 promotes invasion of breast cancer cells through activating Akt signaling pathway

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