Cell Density Regulates Cancer Metastasis Via the Hippo Pathway

Sharif, Ghada M.; Wellstein, Anton

doi:10.2217/fon.15.268

Cited by 24 publications

(22 citation statements)

References 46 publications

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“…However, without the suppressive functions of MST, unphosphorylated YAP gathers in the nucleus and interacts with transcriptional enhancer factor domain (TEAD) transcription factors. This in turn regulates the Mst/Yap pathway via downstream genes that include cysteine rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), survivin (BIRC5) and cyclin D1 (CCND1) ( 15 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

Suppression of YAP by DDP disrupts colon tumor progression

Guo

et al. 2018

Oncol Rep

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Colon cancer is a commonly diagnosed cancer that often has a poor prognosis. Combined with the development of drug resistance to cancer treatment agents the treatment efficacy of colon cancer can be limited. Activation of the oncogene YAP has been shown to be related to colon cancer progression and is associated with poor prognosis, drug resistance and metastasis, even under treatment. Cisplatin (DDP) is a commonly used drug that can control carcinoma progression, although its mechanisms are poorly understood. In the present study, we examined whether DDP specifically suppressed YAP in order to inhibit colon carcinoma progression. Our data revealed that Mst/Yap signaling was unusually activated in colon cancers, promoting cell proliferation and invasion. DDP treatment decreased the expression of YAP at both the transcriptional and post-translational levels, leading to cell cycle arrest, apoptosis and senescence in cancer cells, in addition to decreasing epithelial-to-mesenchymal transition, cell motility and in vitro cell invasion and migration. Ultimately, DDP increased the expression of E-cadherin and decreased the expression of vimentin. The present study also revealed that post-translational regulation of YAP phosphorylation controlled the subcellular distribution between the nucleus and the cytoplasm. In conclusion, the findings of the present study revealed that DDP was a suitable therapeutic candidate for colon cancer that specifically targets the Mst/Yap signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Suppression of YAP by DDP disrupts colon tumor progression

Guo

et al. 2018

Oncol Rep

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“…Interestingly, examination of the migrating cancer cells indicated that the EMT was particularly pronounced in the cancer cells located at the 'invasive front' while confluent BT-474 cells displayed reduced or delayed EMT. This phenomenon has been noticed in other cell types [35][36][37][38][39].…”

Section: Discussionsupporting

confidence: 64%

Cooperativity between stromal cytokines drives the invasive migration of human breast cancer cells

Elisha

Sagi

Klein

et al. 2019

Phil. Trans. R. Soc. B

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The cross-talk between cancer cells and the stromal microenvironment plays a key role in regulating cancer invasion. Here, we employed an ex vivo invasion model system for exploring the regulation of breast cancer cells infiltration into a variety of stromal fibroblast monolayers. Our results revealed considerable variability in the stromal induction of invasiveness, with some lines promoting and others blocking invasion. It was shown that conditioned medium (CM), derived from invasion-promoting fibroblasts, can induce epithelial–mesenchymal transition-like process in the cancer cells, and trigger their infiltration into a monolayer of invasion-blocking fibroblasts. To identify the specific invasion-promoting molecules, we analysed the cytokines in stimulatory CM, screened a library of purified cytokines for invasion-promoting activity and tested the effect of specific inhibitors of selected cytokine receptors on the CM-induced invasion. Taken together, these experiments indicated that the invasiveness of BT-474 is induced by the combined action of IL1 and IL6 and that IL1 can induce IL6 secretion by invasion-blocking fibroblasts, thereby triggering cancer cell invasion into the stroma. This unexpected observation suggests that stromal regulation of cancer invasion may involve not only cross-talk between stromal and cancer cells, but also cooperation between different stromal subpopulations. This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.

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“…Yet, we do not know the source of the signal that would activate the pathway, either Vein or Spitz (Shilo, 2005). We do not understand either how the pathway could be slowed down; by changes in the expression of agonists, antagonists, or the receptor itself, or by chemical (Hariharan & Bilder, 2006;Kango-Singh & Singh, 2009;Fernandez & Kenney, 2010;Kim et al, 2011;Gumbiner & Kim, 2014;Sharif & Wellstein, 2015) or mechanical inhibition of growth. We do not understand either how the pathway could be slowed down; by changes in the expression of agonists, antagonists, or the receptor itself, or by chemical (Hariharan & Bilder, 2006;Kango-Singh & Singh, 2009;Fernandez & Kenney, 2010;Kim et al, 2011;Gumbiner & Kim, 2014;Sharif & Wellstein, 2015) or mechanical inhibition of growth.…”

Section: Cell Proliferation and Shape Changes Direct Histoblast Nest mentioning

confidence: 99%

“…It does not originate in the LECs, as this will lead to more divisions in peripheral than in central histoblasts, when it is not the case (Appendix Fig S4), and it will probably be autocrine. We do not understand either how the pathway could be slowed down; by changes in the expression of agonists, antagonists, or the receptor itself, or by chemical (Hariharan & Bilder, 2006;Kango-Singh & Singh, 2009;Fernandez & Kenney, 2010;Kim et al, 2011;Gumbiner & Kim, 2014;Sharif & Wellstein, 2015) or mechanical inhibition of growth. Further questions arise when focusing in the dynamics and anisotropy of the nests' growth rate.…”

Section: Cell Proliferation and Shape Changes Direct Histoblast Nest mentioning

confidence: 99%

Mechanical coordination is sufficient to promote tissue replacement during metamorphosis in Drosophila

et al. 2019

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During development, cells coordinate to organize in coherent structures. Although it is now well established that physical forces are essential for implementing this coordination, the instructive roles of mechanical inputs are not clear. Here, we show that the replacement of the larval epithelia by the adult one in Drosophila demands the coordinated exchange of mechanical signals between two cell types, the histoblasts (adult precursors) organized in nests and the surrounding larval epidermal cells (LECs). An increasing stress gradient develops from the center of the nests toward the LECs as a result of the forces generated by histoblasts as they proliferate and by the LECs as they delaminate (push/pull coordination). This asymmetric radial coordination of expansive and contractile activities contributes to epithelial replacement. Our analyses support a model in which cell-cell mechanical communication is sufficient for the rearrangements that implement epithelial morphogenesis.

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Cell Density Regulates Cancer Metastasis Via the Hippo Pathway

Cited by 24 publications

References 46 publications

Suppression of YAP by DDP disrupts colon tumor progression

Suppression of YAP by DDP disrupts colon tumor progression

Cooperativity between stromal cytokines drives the invasive migration of human breast cancer cells

Mechanical coordination is sufficient to promote tissue replacement during metamorphosis in Drosophila

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