scholarly journals Distinct roles of AKT isoforms in regulating β1-integrin activity, migration, and invasion in prostate cancer

2012 ◽  
Vol 23 (17) ◽  
pp. 3357-3369 ◽  
Author(s):  
Reetta Virtakoivu ◽  
Teijo Pellinen ◽  
Juha K. Rantala ◽  
Merja Perälä ◽  
Johanna Ivaska
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cell Migration ◽  
Tyrosine Kinases ◽  
Migration And Invasion ◽  
Β1 Integrin ◽  
Akt Isoforms ◽  
Feedback Suppression ◽  
Cancer Migration ◽  
Β1 Integrins

AKT1 and AKT2 kinases have been shown to play opposite roles in breast cancer migration and invasion. In this study, an RNA interference screen for integrin activity inhibitors identified AKT1 as an inhibitor of β1-integrin activity in prostate cancer. Validation experiments investigating all three AKT isoforms demonstrated that, unlike in breast cancer, both AKT1 and AKT2 function as negative regulators of cell migration and invasion in PC3 prostate cancer cells. Down-regulation of AKT1 and AKT2, but not AKT3, induced activation of cell surface β1-integrins and enhanced adhesion, migration, and invasion. Silencing of AKT1 and AKT2 also resulted in increased focal adhesion size. Importantly, the mechanisms involved in integrin activity regulation were distinct for the two AKT isoforms. Silencing of AKT1 relieved feedback suppression of the expression and activity of several receptor tyrosine kinases, including EGFR and MET, with established cross-talk with β1-integrins. Silencing of AKT2, on the other hand, induced up-regulation of the microRNA-200 (miR-200) family, and overexpression of miR-200 was sufficient to induce integrin activity and cell migration in PC3 cells. Taken together, these data define an inhibitory role for both AKT1 and AKT2 in prostate cancer migration and invasion and highlight the cell type–specific actions of AKT kinases in the regulation of cell motility.

MiR-375 Enriched in Bone Marrow Mesenchymal Stem Cells (BMSC) Exosomes Inhibits Prostate Cancer Cell Migration and Invasion by Down-Regulating Trefoil Factor 3 (TFF3)

2021 ◽  
Vol 11 (12) ◽  
pp. 2407-2414
Author(s):  
Qihong Liang ◽  
Wei Zhong
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Cell Migration And Invasion ◽  
Marrow Mesenchymal Stem Cells ◽  
Proliferation And Metastasis

To study the effect and mechanism of miR-375 enriched in BMSC exosomes on prostate cancer (PC) cells. Bioinformatics assessed the potential regulatory miRNA of TFF3 and miR-375 level in breast cancer cells and breast cancer clinical samples was detected by PCR. Dual luciferase assay validated the relationship between TFF3 and miR-375. miR-375 mimics or sh-TFF3 was transfected into PC cells, followed by measuring miR-375 and TFF3 by PCR and Western-blot. Cell proliferation, invasion, migration and apoptosis by Edu staining, transwell and flow cytometry. The BMSC exosomes were then isolated and co-cultured with PC cells to detect cell proliferation and invasion. PC cells and tissues showed the expression of miR-375 was decreased, indicated that miR-375 specifically inhibited TFF3 level. miR-375 was enriched in MSC-derived exosomes and could be transferred to PC cells. miR-375 mimics, exosome miR-375 or silenced TFF3 inhibited TFF3 level, up-regulated PCNA, MMP-2/9 expression, thereby inhibiting cell proliferation and metastasis, and promoting cell apoptosis. miR-375 is enriched in BMSC exosomes and inhibits PC cell migration and invasion by reducing TFF3.

Circular RNA circVAPA regulates breast cancer cell migration and invasion via sponging miR-130a-5p

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 303-317 ◽  
Author(s):  
Si-ying Zhou ◽  
Wei Chen ◽  
Su-jin Yang ◽  
Jian Li ◽  
Jun-ying Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Mirna Sponge ◽  
Cell Migration And Invasion ◽  
Cancer Migration ◽  
Cancer Tissues ◽  
The Relationship

Aim: We aimed to explore the roles of circular RNA, circVAPA in regulating cell migration and invasion of breast cancer. Materials & methods: CircVAPA expression was detected in breast cancer tissues and cells. The role of circVAPA was evaluated by MTT assay, wound-healing and transwell assay. The relationship between circVAPA and miR-130a-5p and the location of circVAPA were explored. Results: We discovered that circVAPA was dysregulated in breast cancer tissues and cells. Ectopic circVAPA regulated breast cancer migration, invasion and proliferation. CircVAPA was mainly expressed in the cytoplasm and could act as a miRNA sponge for miR-130a-5p, but did not regulate its parental gene. Conclusion: CircVAPA may promote migration and invasion capacity of breast cancer via harboring miR-130a-5p.

scholarly journals Rabgap1 promotes recycling of active β1 integrins to support effective cell migration

2020 ◽  
Vol 133 (18) ◽  
pp. jcs243683
Author(s):  
Anna V. Samarelli ◽  
Tilman Ziegler ◽  
Alexander Meves ◽  
Reinhard Fässler ◽  
Ralph T. Böttcher
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Adhesion Formation ◽  
Migration And Invasion ◽  
Β1 Integrin ◽  
Mouse Fibroblasts ◽  
Endosomal Recycling ◽  
Focal Adhesion Formation ◽  
Β1 Integrins ◽  
Npxy Motif

ABSTRACTIntegrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role for Rabgap1 (GAPCenA) in the recycling of endocytosed active β1 integrins to the plasma membrane. The phosphotyrosine-binding (PTB) domain of Rabgap1 binds to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunits on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesion formation, and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Taken together, our results identify Rabgap1 as an important factor for conformation-specific integrin trafficking and define the role of Rabgap1 in β1-integrin-mediated cell migration in mouse fibroblasts and breast cancer cells.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Pradip Shahi Thakuri ◽  
Megha Gupta ◽  
Sunil Singh ◽  
Ramila Joshi ◽  
Eric Glasgow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Protein Kinases ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Tnbc Cell

Abstract Background Cell migration and invasion are essential processes for metastatic dissemination of cancer cells. Significant progress has been made in developing new therapies against oncogenic signaling to eliminate cancer cells and shrink tumors. However, inherent heterogeneity and treatment-induced adaptation to drugs commonly enable subsets of cancer cells to survive therapy. In addition to local recurrence, these cells escape a primary tumor and migrate through the stroma to access the circulation and metastasize to different organs, leading to an incurable disease. As such, therapeutics that block migration and invasion of cancer cells may inhibit or reduce metastasis and significantly improve cancer therapy. This is particularly more important for cancers, such as triple negative breast cancer, that currently lack targeted drugs. Methods We used cell migration, 3D invasion, zebrafish metastasis model, and phosphorylation analysis of 43 protein kinases in nine triple negative breast cancer (TNBC) cell lines to study effects of fisetin and quercetin on inhibition of TNBC cell migration, invasion, and metastasis. Results Fisetin and quercetin were highly effective against migration of all nine TNBC cell lines with up to 76 and 74% inhibitory effects, respectively. In addition, treatments significantly reduced 3D invasion of highly motile TNBC cells from spheroids into a collagen matrix and their metastasis in vivo. Fisetin and quercetin commonly targeted different components and substrates of the oncogenic PI3K/AKT pathway and significantly reduced their activities. Additionally, both compounds disrupted activities of several protein kinases in MAPK and STAT pathways. We used molecular inhibitors specific to these signaling proteins to establish the migration-inhibitory role of the two phytochemicals against TNBC cells. Conclusions We established that fisetin and quercetin potently inhibit migration of metastatic TNBC cells by interfering with activities of oncogenic protein kinases in multiple pathways.

A fluorescence nanoprobe for detecting the effect of different oxygen and nutrient conditions on breast cancer cells migration and invasion

2021 ◽  
Author(s):  
Ping Zhou ◽  
Bo Liu ◽  
Mingming Luan ◽  
Na Li ◽  
Bo Tang
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Fluorescence Nanoprobe

Cancer cell migration and invasion are initial steps for tumor metastasis that increases patient mortality. Tumor microenvironment is characterized by hypoxic and low nutrient-containing. Previous studies have suggested that hypoxia...

scholarly journals ATM-Mediated Phosphorylation of Cortactin Involved in Actin Polymerization Promotes Breast Cancer Cells Migration and Invasion

2018 ◽  
Vol 51 (6) ◽  
pp. 2972-2988 ◽  
Author(s):  
Lei Lang ◽  
Yixuan Hou ◽  
Yanlin Chen ◽  
Gang Tu ◽  
Jing Tao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Actin Polymerization ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Transwell Assay ◽  
Atm Kinase ◽  
Cell Migration And Invasion

Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization.

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