Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin.

Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin. Oncotarget. 2018 Jan 19;9(5):5545-5561 Authors: Dybdal-Hargreaves NF, Risinger AL, Mooberry SL Abstract Microtubule targeting agents (MTAs) are some of the most effective anticancer drugs used to treat a wide variety of adult and pediatric cancers. Building evidence suggests that these drugs inhibit interphase signaling events and that this contributes to their anticancer actions. The effects of diverse MTAs were evaluated following a 2 hour incubation with clinically relevant concentrations to test the hypothesis that these drugs rapidly and differentially disrupt epithelial-to-mesenchymal transition (EMT)-related signaling. The MTAs rapidly promoted the cortical localization of internal pools of E-cadherin in HCC1937 breast cancer cells, with the most robust effects observed with the microtubule destabilizers eribulin and vinorelbine. Cortical E-cadherin localization was also promoted by the Src kinase inhibitor dasatinib or by siRNA-mediated depletion of the p130Cas scaffold. Mechanistic studies demonstrate that eribulin disrupts the interaction between p130Cas and Src, leading to decreased cortical Src phosphorylation that precedes the accumulation of cortical E-cadherin. These results suggest that microtubules can be actively co-opted by cancer cells to inhibit cortical E-cadherin localization, a ha...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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Augusto Orlandi Breast cancer is the most common form of tumor in women and the leading cause of cancer-related mortality. Even though the major cellular burden in breast cancer is constituted by the so-called bulk tumor cells, another cell subpopulation named cancer stem cells (CSCs) has been identified. The latter have stem features, a self-renewal capacity, and the ability to regenerate the bulk tumor cells. CSCs have been described in several cancer types but breast cancer stem cells (BCSCs) were among the first to be identified and characterized. Therefore, many efforts have been put into the phenotypic character...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells in vitro, and tumor growth in vivo. Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion in vitro, and reduced tumor growth in xenograft mo...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
e;lez Samuel Cos Carolina Alonso-González Carlos Martínez-Campa Melatonin mitigates cancer initiation, progression and metastasis through inhibition of both the synthesis of estrogens and the transcriptional activity of the estradiol-ER (Estrogen receptor) complex in the estrogen-dependent breast cancer cell line MCF-7. Moreover, melatonin improves the sensitivity of MCF-7 to chemotherapeutic agents and protects against their side effects. It has been described that melatonin potentiates the anti-proliferative effects of doxorubicin; however, the molecular changes involving gene expression and the a...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA overexpressed in various cancers that promotes cell growth and metastasis. Although hypoxia has been shown to up-regulate MALAT1, only hypoxia-inducible factors (HIFs) have been implicated in activation of the MALAT1 promoter in specific cell types and other molecular mechanisms associated with hypoxia-mediated MALAT1 up-regulation remain largely unknown. Here, we demonstrate that hypoxia induces cancer cell-specific chromatin–chromatin interactions between newly identified enhancer-like cis-regulatory elements present at the MALA...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Gene Regulation Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Contributor : Akira OrimoSeries Type : Expression profiling by arrayOrganism : Homo sapiensEmerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. However, whether tumor-associated stroma induces epithelial-mesenchymal plasticity in tumor cell clusters, to promote invasion and metastasis, remains unknown. We demonstrate herein that carcinoma-associated fibroblasts (CAFs) frequently present in tumor stroma drive the formation of tumor cell clusters composed of two distinct cancer cell populations, one in a highly-epithelial (E-cadherin-high ZEB1-low/neg: E-hi) state and anothe...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Abstract Long non-coding RNAs (lncRNAs) regulate cancer development and progression. Here, we investigated the role of the lncRNA CCAT1 in triple-negative breast cancer (TNBC). CCAT1 expression was higher in TNBC cells than normal breast epithelial cells. Additionally, CCAT1 expression was higher in TNBC patient tumor tissue than adjacent normal breast tissue. Silencing CCAT1 inhibited TNBC cell proliferation, migration, and invasion in vitro, and tumor growth and progression in vivo. Bioinformatics analysis revealed that microRNA-218 (miR-218) is a potential target of CCAT1. Silencing CCAT1 resulted in an increas...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Publication date: Available online 13 July 2019Source: Seminars in Cancer BiologyAuthor(s): Zoi Piperigkou, Nikos K. KaramanosAbstractThe biological functions of estrogens are regulated by estrogen receptors (ERα and ERβ), which contribute in the progression of several hormone-responsive cancer types via estrogen signaling mechanisms. The coordinated actions of ERs and extracellular matrix (ECM) macromolecules are principal mediators of ECM remodeling in the tumor and the adjacent stroma. In breast cancer, ERs are critical biomarkers as their expression in breast tumor determines the disease-free survival, yet g...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
Conclusion: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients. PMID: 31281728 [PubMed]
Source: Journal of Breast Cancer - Category: Cancer & Oncology Tags: J Breast Cancer Source Type: research
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