Leptin-induced Epithelial-Mesenchymal Transition in Breast Cancer Cells Requires β-Catenin Activation via Akt/GSK3- and MTA1/Wnt1 Protein-dependent Pathways

Yan, Dan; Avtanski, Dimiter; Saxena, Neeraj K.; Sharma, Dipali

doi:10.1074/jbc.m111.322800

Cited by 171 publications

(165 citation statements)

References 63 publications

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“…Cellular signaling pathways, including the Wnt/β-catenin, ERK/MAPK, and PI3K/ Akt pathways, have been found to be aberrantly activated and play vital roles in the development and progression of breast cancer (35)(36)(37). Among these pathways, the prometastatic functions of Wnt/β-catenin signaling in breast cancer have been well documented (35,38). Notably, unlike in other cancer types, the mutations in β-catenin are rare, but the expression and/or nuclear localization of β-catenin is often abnormal in breast cancer, indicating a constitutive activation of Wnt/β-catenin signaling (9,39,40).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

Cai¹,

Guan²,

Fang³

et al. 2013

J. Clin. Invest.

261

281

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Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

Cai¹,

Guan²,

Fang³

et al. 2013

J. Clin. Invest.

261

281

View full text Add to dashboard Cite

show abstract

“…However, when this pathway is activated, GSK3β phosphorylates β-catenin, triggering its ubiquitination and subsequent proteasomemediated degradation. Therefore, GSK3β regulates EMT and metastasis via its phosphorylation by AKT [111]. Melatonin, by inhibition of AKT, leads to inhibition of EMT and the development of a metastatic phenotype [112].…”

Section: Antimetastatic Effectsmentioning

confidence: 99%

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Cardinali¹,

Escames²,

Acuña-Castroviejo³

et al. 2016

J Integr Oncol

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“…In addition to activating cell proliferation, leptin also poses a risk to breast cancer patients through its ability to influence epithelial to mesenchymal transition (EMT). Yan et al (2012) demonstrated that leptin increases beta-catenin levels which are essential for promoter recruitment which leads to leptin-induced EMT and tumor formation. Beta-catenin levels are increased through leptin-induced phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) by both activated Akt and by activation of Wnt signaling through MTA1 (Yan et al, 2012).…”

Section: Obesitymentioning

confidence: 99%

Mechanics behind Breast Cancer Prevention - Focus on Obesity, Exercise and Dietary Fat

Alegre¹,

Knowles²,

Robison³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Cancer prevention is rapidly emerging as a major strategy to reduce cancer mortality. In the field of breast cancer, significant strides have recently been made in the understanding of underlying preventive mechanisms. Currently, three major strategies have been linked to an increase in breast cancer risk: obesity, lack of physical exercise, and high levels of saturated dietary fat. As a result, prevention strategies for breast cancer are usually centered on these lifestyle factors. Unfortunately, there remains controversy regarding epidemiological studies that seek to determine the benefit of these lifestyle changes. We have identified crucial mechanisms that may help clarify these conflicting studies. For example, recent reports with olive oil have demonstrated that it may influence crucial transcription factors and reduce breast tumor aggressiveness by targeting HER2. Similarly, physical exercise reduces sex hormone levels, which may help protect against breast cancer. Obesity promotes tumor cell growth and cell survival through upregulation of leptin and insulin-like growth factors. This review seeks to discuss these underlying mechanisms, and more behind the three major prevention strategies, as a means of understanding how breast cancer can be prevented.

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Leptin-induced Epithelial-Mesenchymal Transition in Breast Cancer Cells Requires β-Catenin Activation via Akt/GSK3- and MTA1/Wnt1 Protein-dependent Pathways

Cited by 171 publications

References 63 publications

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Mechanics behind Breast Cancer Prevention - Focus on Obesity, Exercise and Dietary Fat

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