Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway

Wang, Yingmei; Zhu, Yuanxi; Zhang, Lizhi; Tian, Wenyan; Hua, Surong; Zhao, Jing; Zhang, Huiying; Xue, Fengxia

doi:10.1016/j.canlet.2012.03.026

Cited by 37 publications

(37 citation statements)

References 39 publications

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“…IGF1 and IGF2 are strong mitogens that exert proliferative and anti-apoptotic effects via 2 downstream signaling pathways, the MAPK/ERK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B cascades (2). The IR, IRS1/2 and MAPK/ERK1/2 signaling pathways have all been revealed to be highly expressed in EC (19,21).…”

Section: Discussionmentioning

confidence: 99%

“…The IGF-1 pathway has been revealed to modulate cell apoptosis, while the MAPK/ERK pathway has been implicated in cell proliferation (2). The IGF-1R signaling pathway is initiated upon the binding of IGF-1 to its cell-surface IGF-1R to activate the MAPK/ERK signaling pathway (24).…”

Section: Discussionmentioning

confidence: 99%

“…High insulin levels and obesity are independent risk factors for estrogen-related type I endometrial endometrioid carcinomas (2). At present, surgery combined with adjuvant progesterone therapy or postsurgical radiotherapy is the predominant treatment strategy for endometrial cancer (3).…”

Section: Introductionmentioning

confidence: 99%

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Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

et al. 2017

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Abstract. Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways. Furthermore, the forkhead box protein O1 pathway was upregulated, while the IGF1 receptor, insulin receptor substrate 1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit b pathways were downregulated. Carcinoma tumorigenesis, tumor cell mitosis and tumor cell death were significantly upregulated disease states and functions, while cell proliferation and tumor growth were significantly downregulated. The results of the present study suggested that ARID1A may be a potential prognostic and therapeutic molecular drug target for the prevention of EC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

et al. 2017

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“…The ERK signaling pathway plays a crucial role in regulating the proliferation, survival and invasion of EC (22,23). The synthesis of MMP-2 and -9 is regulated by a number of signaling pathways, including the ERK signaling pathway (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

et al. 2015

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Abstract. Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signalregulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC.

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“…Further confirmation was achieved with assessment of mRNA levels of EMT genes such as E-Cadherin, Vimentin, Zeb1, Snail and FOXC2 ( Figure 3). Consistently, insulin has previously been reported as a direct promoter of invasion and migration of different cancer cells in vitro [333,334]. Therefore, the expression of these genes in circulating tumour cells will be monitored in the clinical trial, to correlate with patient outcome.…”

Section: Rationalementioning

confidence: 59%

Androgen Deprivation Therapy (ADT), Metabolic Syndrome and Metastatic Prostate Cancer: In Vivo and In Vitro Assessments of Effects of Metformin

Rhee¹

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Research Title -In vivo In this translational research PhD project, we conducted a randomized, placebo-controlled clinical trial named ADT and Adjuvant Metformin (ADMET) trial to determine the metabolic and therapeutic effects of treating hyperinsulinaemia in men starting ADT using a diabetic medication called metformin. Men who had been diagnosed with metastatic PCa and commencing ADT as a standard strategy provided the opportunity to study the physiological and pathological impact of the acute rise in insulin levels resulting from the iatrogenic hypogonadism [6]. To assess for the therapeutic benefits of metformin, we used a variety of novel technologies such as circulating tumour cell (CTC) enumeration, culture, transcriptomic analysis, and molecular imaging.The clinical trial was commenced in September 2014 and was completed in March 2017. It concluded that hyperinsulinaemia and MS is a phenomenon that affects most patients when using ADT, although the changes can be ameliorated by metformin. The use of medication was associated with the reduced need for treatment of MS with agents such as statins and progression to CRPC. Further, the trial confirmed that insulin resistance at the time of starting treatment is associated with early development of CRPC and progression of the disease.Progression free survival was also demonstrated using a novel molecular imaging called Prostate Specific

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Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway

Cited by 37 publications

References 39 publications

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

Androgen Deprivation Therapy (ADT), Metabolic Syndrome and Metastatic Prostate Cancer: In Vivo and In Vitro Assessments of Effects of Metformin

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