Abstract 4052: Targeting PDK1 in breast cancer: kinase-dependent regulation of tumor growth and kinase-independent regulation of cell migration and invasion

2014 ◽  
Author(s):  
Paolo Armando Gagliardi ◽  
Laura di Blasio ◽  
Giorgio Seano ◽  
Roberto Sessa ◽  
Alberto Puliafito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

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 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.

scholarly journals SPDEF targets EMT pathway to inhibit cell migration and invasion in triple‐negative breast cancer

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Hassan Yousefi ◽  
Mousa Vatanmakanian ◽  
Sweaty Koul ◽  
Samuel Okpechi ◽  
Suresh Alahari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

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.

scholarly journals Acetylation of ezrin regulates membrane–cytoskeleton interaction underlying CCL18-elicited cell migration

2019 ◽  
Vol 12 (6) ◽  
pp. 424-437 ◽  
Author(s):  
Xiaoyu Song ◽  
Wanjuan Wang ◽  
Haowei Wang ◽  
Xiao Yuan ◽  
Fengrui Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Lipid Binding ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
Breast Cancer Cell Migration ◽  
Membrane Cytoskeleton

Abstract Ezrin, a membrane–cytoskeleton linker protein, plays an essential role in cell polarity establishment, cell migration, and division. Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by promoting cancer cell survivor and promotes intrahepatic metastasis via cell migration. However, it was less characterized whether there are additional post-translational modifications and/or post-translational crosstalks on ezrin underlying context-dependent breast cancer cell migration and invasion. Here we show that ezrin is acetylated by p300/CBP-associated factor (PCAF) in breast cancer cells in response to CCL18 stimulation. Ezrin physically interacts with PCAF and is a cognate substrate of PCAF. The acetylation site of ezrin was mapped by mass spectrometric analyses, and dynamic acetylation of ezrin is essential for CCL18-induced breast cancer cell migration and invasion. Mechanistically, the acetylation reduced the lipid-binding activity of ezrin to ensure a robust and dynamic cycling between the plasma membrane and cytosol in response to CCL18 stimulation. Biochemical analyses show that ezrin acetylation prevents the phosphorylation of Thr567. Using atomic force microscopic measurements, our study revealed that acetylation of ezrin induced its unfolding into a dominant structure, which prevents ezrin phosphorylation at Thr567. Thus, these results present a previously undefined mechanism by which CCL18-elicited crosstalks between the acetylation and phosphorylation on ezrin control breast cancer cell migration and invasion. This suggests that targeting PCAF signaling could be a potential therapeutic strategy for combating hyperactive ezrin-driven cancer progression.

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