Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways

Zhang, Zhenbo; Zhou, Dongmei; Lai, Yunli; Liu, Yongjuan; Tao, Xiang; Wang, Qianqian; Zhao, Guixu; Gu, Hongqin; Liao, Hong; Zhu, Yue; Xi, Xiaowei; Yan, Feng

doi:10.1016/j.canlet.2011.12.033

Cited by 91 publications

(67 citation statements)

References 31 publications

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“…42, 43 Adipose tissue is an important source of estrogen 44 and estrogen induces proliferation of endometrial and breast (post-menopausal) cancer cells. 45, 46 Considering that insulin, IGF-1, and estrogen have been identified as risk factors for obesity-linked cancers, perhaps it could be that obesity promotes cancer cell proliferation at least in part through obesity-initiated metabolic syndrome. Inflammatory responses are characterized by an increase of cytokines and markers of active inflammation (C-reactive protein and fibrinogen).…”

Section: Discussionmentioning

confidence: 99%

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer, obesity‐linked cancers and breast cancer among women in NHANES III

Gathirua-Mwangi

Song

Monahan

et al. 2018

Intl Journal of Cancer

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Although metabolic syndrome (MetS) is a prognostic factor for cancer occurrence, the association of MetS and cancer mortality remains unclear. The purpose of this study was to evaluate whether MetS, components of MetS and C-reactive protein (CRP) are associated with cancer mortality in women. A total of 400 cancer deaths, with 140 deaths from obesity-linked-cancers (OLCas), [breast (BCa), colorectal, pancreatic and endometrial], linked through the National Death Index, were identified from 10,104 eligible subjects aged ≥18 years. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for cancer mortality. MetS was associated with increased deaths for total cancer [HR = 1.33, 95% confidence interval (CI) 1.04-1.70] and BCa [HR = 2.1, 95% CI, 1.09-4.11]. The risk of total cancer [HR = 1.7, 95% CI, 1.12-2.68], OLCas [HR = 2.1, 95% CI, 1.00-4.37] and BCa [HR = 3.8, 95% CI, 1.34-10.91] mortality was highest for women with all MetS components abnormal, compared to those without MetS. Linear associations of blood-pressure [HR = 2.5, 1.02-6.12, Quartile (Q) 4 vs Q1, p trend = 0.004] and blood-glucose [HR = 2.2, 1.04-4.60, Q4 vs. Q1, p trend = 0.04] with total-OLCas mortality were observed. A threefold increased risk of BCa mortality was observed for women with enlarged waist circumference, ≥100.9 cm, [HR = 3.5, 1.14-10.51, p trend = 0.008] and in those with increased blood glucose, ≥101 mg/dL, [HR = 3.2, 1.11-9.20, p trend = 0.03] compared to those in Q1. None of the components of MetS were associated with total-cancer mortality. CRP was not associated with cancer mortality. In conclusion, MetS is associated with total-cancer and breast-cancer mortality, with waist circumference, blood pressure and blood glucose as independent predictors of OLCas and BCa mortality.

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Section: Discussionmentioning

confidence: 99%

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer, obesity‐linked cancers and breast cancer among women in NHANES III

Gathirua-Mwangi

Song

Monahan

et al. 2018

Intl Journal of Cancer

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“…The sequences were as follows: siLSD1-1, CCACGAGUCAAACCUUUAUTT, AUAAAGGUUUGACUCGUGGTT; siLSD1-2: GCCACCCAGAGAUAUUACUTT, AGUAAUAUCU CUGGGUGGCTT. The acute siRNA and stable shRNA plasmid transfection experiments were performed as previously described [56]. LSD1 shRNA constructs were obtained from Professor Xiaobing Shi at the Center for Epigenetics in the UT M.D.…”

Section: Methodsmentioning

confidence: 99%

LSD1 binds to HPV16 E7 and promotes the epithelial-mesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

et al. 2016

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Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.

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“…These observations suggest that certain exogenous factors in conjunction with genetic predisposition can alter host susceptibility to carcinogenesis. In view of these observations, we conducted a retrospective study with the objective of estimating the association between MetS and PMBC; in addition, we evaluated the potential association of variants (SNPs) of eight genes which have been implicated in harboring susceptibility to adiposity, inflammation and cell proliferation (Frayling et al 2007; Kakamani et al 2011; Hunter et al 2007; Dossus et al 2008; Langsenlehner et al 2006; Zhang et al 2012; Healey et al 2011; Dossus et al 2010; Stacey et al 2007; Andreasen et al 2008; Rebbeck et al 2009; Easton et al 2007; Brasky et al 2011). …”

Section: Introductionmentioning

confidence: 99%

Adiposity, inflammation, genetic variants and risk of post-menopausal breast cancer findings from a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design approach

et al. 2013

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Chronic internal inflammation secondary to adiposity is a risk factor for sporadic breast cancer and Post-Menopausal Breast Cancer (PMBC) is largely defined as such. Adiposity is one of the clinical criteria for the diagnosis of Metabolic Syndrome (MetS) and is a risk factor for PMBC. We examined SNPs of eight genes implicated in adiposity, inflammation and cell proliferation in a Prospective-specimen-collection, Retrospective-Blinded-Evaluation (PRoBE) design approach. A total of 180 cases and 732 age-matched controls were identified from the MyCode prospective biobank database and then linked to the Clinical Decision Information System, an enterprise-wide data warehouse, to retrieve clinico-demographic data. Samples were analyzed in a core laboratory where the personnel were masked to their status. Results from multivariate logistic regression yielded one SNP (rs2922126) in the GHSR as protective against PMBC among homozygotes for the minor allele (A/A) (OR = 0.4, 95% CI 0.18-.89, P-value = .02); homozygosity for the minor allele (C/C) of the SNP (rs889312) of the gene MAP3K1 was associated with the risk of PMBC (OR = 2.41, 95% CI 1.25-4.63 P-value = .008). Advanced age was protective against PMBC (OR = 0.98, 95% CI 0.95-0.99, P-value = .02). Family history of breast cancer (OR = 2.22, 95% CI 1.14-4.43. P = .02), HRT (OR = 3.35; 95% CI 2.15-5.21, P < .001), and MetS (OR = 14.83, 95% CI 5.63-39.08, P < .001) and interaction between HRT and MetS (OR = 39.38, 95% CI 15.71-98.70, P < .001) were associated with the risk of PMBC. We did not detected significant interactions between SNPs or between the SNPs and the clinico-demographic risk factors. Our study further confirms that MetS increases the risk of PMBC and argues in favor of reducing exposure to HRT. Our findings are another confirmation that low penetrance genes involved in the inflammatory pathway, i.e. MAP3KI gene, may have a plausible causative role in PMBC. Given the fact that genetic constitutionality of individuals cannot be changed, efforts should be focused on life style modification.

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Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways

Cited by 91 publications

References 31 publications

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer, obesity‐linked cancers and breast cancer among women in NHANES III

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer, obesity‐linked cancers and breast cancer among women in NHANES III

LSD1 binds to HPV16 E7 and promotes the epithelial-mesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

Adiposity, inflammation, genetic variants and risk of post-menopausal breast cancer findings from a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design approach

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