Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Li, Juan; Liu, Jie; Yang, Jin Ming; Li, Pingping; Mao, Xiaona; Li, Wenjie; Liu, Peijun

doi:10.1186/preaccept-6783991421275553

Cited by 27 publications

(31 citation statements)

References 33 publications

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“…The parent of the LCC6 cells, the MDA-MB-435 cell line, is highly metastatic and expresses many of the classic EMT markers such as low levels of E-cadherin and high levels of Vimentin, N-cadherin, and alpha smooth muscle actin (Li, et al 2014; Manni, et al 2002). In the current study, we show down-regulated expression of mesenchymal markers including Vimentin, TWIST1, SLUG (SNAIL family transcription factor) and ZEB1 at RNA and protein levels in the tumors with IR knockdown.…”

Section: Discussionmentioning

confidence: 99%

EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

Zelenko

Gallagher

Antoniou

et al. 2016

Endocrine-Related Cancer

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Type 2 Diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing the Rag1−/− mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate the Rag1−/− (Rag/WT) and Rag1−/−/MKR+/+ (Rag/MKR) mice. The female Rag/MKR mice are insulin resistant and have significantly higher non-fasting plasma insulin levels compared to the Rag/WT controls. Therefore, we used these Rag/MKR mice to investigate the role of endogenous hyperinsulinemia on human cancer progression. In this study we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors, TWIST1 and ZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA). We also show that silencing the insulin receptor (IR) in the human LCC6 cancer cells leads to decreased tumor growth and metastases, suppression of mesenchymal markers Vimentin, SLUG, TWIST1, and ZEB1, suppression of angiogenesis markers, VEGFA and VEGFD, and re-expression of the epithelial marker, E-cadherin. The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial-mesenchymal transition.

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Section: Discussionmentioning

confidence: 99%

EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

Zelenko

Gallagher

Antoniou

et al. 2016

Endocrine-Related Cancer

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“…MCF10A cells were cultured as previously described. 57 MCF12A cells were cultured in the same way as the MCF10A cells. The cells were incubated in 5% CO 2 at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

CRB3 regulates contact inhibition by activating the Hippo pathway in mammary epithelial cells

Mao

Wang

et al. 2017

Cell Death Dis

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The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions. Furthermore, we report for the first time that CRB3 acts as an upstream regulator of the Hippo pathway to regulate contact inhibition by recruiting other Hippo molecules, such as Kibra and/or FRMD6, in mammary epithelial cells. In addition, CRB3 inhibits tumour growth in vivo. Collectively, the present study increases our understanding of the Hippo pathway and provides an important theoretical basis for exploring new avenues for breast cancer treatment.

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“…Furthermore, under the stress, energy demand or energy supply imbalance conditions that are typical requirement of the tumor microenvironment leads to increase in the expression of AMPK that alters the cancer cell's flexibility to utilize nutrient glucose directly (Liang and Mills 2013;Herrmann et al 2011). Other studies reported that the knockdown of STK11 in MCF-7 and MDA-MB-435 cells induced migration and invasion of breast cancer cells due to which loss of cell polarity and cell-cell adhesion occurs (Li et al 2014;Zhuang et al 2006).…”

Section: Discussionmentioning

confidence: 99%