The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration

Meng, Fanrui; Saxena, Sandeep; Liu, Youtao; Joshi, Bharat; Wong, Ten It; Shankar, Jata; Foster, Leonard J.; Bernatchez, Pascal; Nabi, Ivan R.

doi:10.1091/mbc.e17-05-0278

Cited by 45 publications

(62 citation statements)

References 85 publications

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“…Cells secrete certain adhesive proteins that fasten cells together and prevent cells from metastasizing to other sites [ 31 ]. The force produced by those adhesive proteins can be measured using AFM; the adhesive force of malignant cancer tissue is lower than normal tissue, so measuring the adhesive force between cells can reflect the metastasizing capacities of tumor cells [ 32 ]. The plasticity or elasticity of cells is the necessary condition of cell migration and Young’s modulus is often used to detect the plasticity or elasticity of cells in bioengineering [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxy-4’-Nitro-7-Propionyloxy-Genistein Inhibited Invasion and Metastasis via Inactivating Wnt/b-Catenin Signal Pathway in Human Endometrial Carcinoma Ji Endometrial Cells

Bai

Luo

2018

Med Sci Monit

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BackgroundChemotherapy has been assuring more important roles in the treatment of carcinoma. Developing new types of drugs with less adverse effects and low drug resistance has become an important researching focus. The present study aimed to investigate the anticancer effects of 5-hydroxy-4′-nitro-7-propionyloxy-genistein (HNPG) and to elucidate its underlying molecular mechanism.Material/MethodsThe inhibitory effects of cell viability of HNPG were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flat plate clone formation method, and Transwell assay. The distribution of cell cycle was analyzed using flow cytometry (FCM) method. The morphological alteration, root-mean-squared roughness (Rq), average roughness (Ra), Young’s modulus, and adhesive force were measured by atomic force microscope (AFM) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to explore the possible molecular mechanism.ResultsWe found that HNPG had dramatic activity against Ji Endometrial cells (JEC) in vitro, inhibited the proliferation and colony formation, attenuated invasion and migration ability, and arrested cell cycle in G1 phase, all in a dose-dependent manner. Simultaneously, cell bodies shrunk, pseudopod structures retracted, Rq and Ra were reduced, and Young’s modulus and adhesive force increased, accompanied by downregulation of β-catenin, C-Myc, Cyclin D1, matrix metalloprotease 2 (MMP-2), matrix metalloprotease 7 (MMP-7), and matrix metalloprotease 9 (MMP-9).ConclusionsHNPG dramatically inhibited invasion and metastasis of JEC cells in vitro. Its molecular mechanism might be related to inactivation of the wnt/β-catenin signal pathway, accumulated cells in G1/S phase, inhibited cell proliferation, improved adhesive force between cells, and reduced cell plasticity and elasticity.

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Section: Discussionmentioning

confidence: 99%

5-Hydroxy-4’-Nitro-7-Propionyloxy-Genistein Inhibited Invasion and Metastasis via Inactivating Wnt/b-Catenin Signal Pathway in Human Endometrial Carcinoma Ji Endometrial Cells

Bai

Luo

2018

Med Sci Monit

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“…MCF7 cells were transfected with Cav1-myc-mRFP or Cav1-F92A/ Y94A myc-mRFP plasmids (Joshi et al 2012;Meng et al 2017), using the HilyMax transfection reagent (No. H357-10, Dojindo Molecular Technologies, USA), according to the manufacturer's protocol, and were selected for G418 resistance.…”

Section: Cell Lines Culture Techniques and Gene Expressionmentioning

confidence: 99%

Effect of caveolin-1 on Stat3-ptyr705 levels in breast and lung carcinoma cells

Geletu

Taha

Arulanandam

et al. 2019

Biochem. Cell Biol.

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We recently demonstrated that Cav1 (caveolin-1) is a negative regulator of Stat3 (signal transducer and activator of transcription-3) activity in mouse fibroblasts and human lung carcinoma SHP77 cells. We now examined whether the cellular context may affect their levels as well as the relationship between them, by assessing Cav1 and Stat3-ptyr705 amounts in different cell lines. In MDA-MB-231, A549, and HaCat cells, Cav1 levels were high and Stat3-ptyr705 levels were low, consistent with the notion of a negative effect of endogenous Cav1 on Stat3-ptyr705 levels in these lines. In addition, manipulation of Cav1 levels revealed a negative effect in MCF7 and mouse fibroblast cells, while Cav1 upregulation induced apoptosis in MCF7 cells. In contrast, however, line MRC9 had high Cav1 and high Stat3-ptyr705 levels, indicating that high Cav1 is insufficient to reduce Stat3-ptyr705 levels in this line. MCF7 and LuCi6 cells had very low Cav1 and Stat3-ptyr705 levels, indicating that the low Stat3-ptyr705 can be independent from Cav1 levels altogether. Our results reveal a further level of complexity in the relationship between Cav1 and Stat3-ptyr705 than previously thought. In addition, we demonstrate that in a feedback loop, Stat3 inhibition upregulates Cav1 in HeLa cells but not in other lines tested.

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“…In the heart, studies in Cav-1 knockout mice suggest that Cav-1/Src interactions are critical to adaptation to ischemic stress and cell-cell communication and arrhythmogenicity . Cav-1 tyrosine 14 is the primary Src phosphorylation target that has been implicated in focal adhesion and cancer biology (Ortiz et al, 2016;Meng et al, 2017), endothelial cell signaling in sepsis-induced lung injury (Jiao et al, 2013), regulation of mechanotransduction (Zhang et al, 2007;Joshi et al, 2012), and insulin signaling (Chen et al, 2008). Additionally, caveolins can undergo S-nitrosylation, which is important in the setting of oxidant stress.…”

Section: Novel Molecular Mechanismsmentioning

confidence: 99%

Caveolins as Regulators of Stress Adaptation

2018

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Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The following review will focus specifically on the role of caveolin in stress adaptation in the heart, brain, and eye, three organs that are susceptible to acute and chronic stress and that show as well declining function with age. In addition, we consider some novel molecular mechanisms that may account for this stress adaptation and also offer potential to drive the future of caveolin research.

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The phospho–caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration

Abstract: The caveolin scaffolding domain mediates the promigratory activity of Src-phosphorylated (on Y14) caveolin-1 and, specifically, regulation of vinculin tension in focal adhesions. This suggests that pY14Cav1 enhances cancer cell migration by promoting engagement of focal adhesion traction.

Cited by 45 publications

References 85 publications

5-Hydroxy-4’-Nitro-7-Propionyloxy-Genistein Inhibited Invasion and Metastasis via Inactivating Wnt/b-Catenin Signal Pathway in Human Endometrial Carcinoma Ji Endometrial Cells

5-Hydroxy-4’-Nitro-7-Propionyloxy-Genistein Inhibited Invasion and Metastasis via Inactivating Wnt/b-Catenin Signal Pathway in Human Endometrial Carcinoma Ji Endometrial Cells

Effect of caveolin-1 on Stat3-ptyr705 levels in breast and lung carcinoma cells

Caveolins as Regulators of Stress Adaptation

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