Mechanisms Of Cancer Cell Invasion
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Mechanisms Of Cancer Cell Invasion
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Author : Tatiana Smirnova
language : en
Publisher:
Release Date : 2010
Mechanisms Of Cancer Cell Invasion written by Tatiana Smirnova and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Molecular Mechanisms Of Cancer Cell Invasion During Metastasis
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Author : Charles Vincent Rajadurai
language : en
Publisher:
Release Date : 2015
Molecular Mechanisms Of Cancer Cell Invasion During Metastasis written by Charles Vincent Rajadurai and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.
"ABSTRACTThe Met receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor (HGF) are potent regulators of epithelial remodeling, dispersal and motility. As such, Met/HGF signaling plays crucial roles in wound healing in the adult and epithelial motility during embryogenesis. In cancer, Met/HGF signaling is often deregulated, and elevated Met activity is associated with increased cancer cell invasion and aggressive tumors with poor patient prognosis. Although the capacity of invasive carcinoma cells to form actin-rich extra cellular matrix (ECM)-remodeling protrusions called invadopodia, has emerged as a major mechanism of cancer cell invasion, prior to this thesis, it was not known whether Met promotes invadopodia formation, and if so, the mechanism.I established that in Met-amplified cancer cells, invadopodia formation is dependent on Met signals and is a key mechanism for cell invasion. Moreover, in invasive carcinoma cells with basal invadopodia forming capacity, ligand, HGF, mediated activation of Met further enhances invadopodia formation. Hence, Met-induced signals may synergize with other oncogenic signals to potentiate cell invasion. Met coordinates invadopodia biogenesis primarily through the scaffold protein Gab1. We identified a novel interaction between Gab1 and cortactin and demonstrated that Gab1-cortactin interaction is essential for Met-dependent invadopodia formation. Met co-localizes with cortactin to invadopodia and promotes cortactin phosphorylation, thus driving localized cytoskeletal changes required for invasive membrane protrusion.Signals downstream from multiple RTKs and integrins are coupled to the actin cytoskeleton through, among other mechanisms, changes in membrane phosphatidylinositol composition. In agreement, PI3K, an enzyme whose activity is frequently elevated in cancers, has been identified as a prerequisite for invadopodia biogenesis. I have identified SHIP2, a 5' inositol phosphatase, as a critical regulator of invadopodia biogenesis. SHIP2 cooperates with PI3K to produce Ptdlns(3,4)P2, a phosphatidylinositol with a key regulatory role in invadopodia assembly. SHIP2 also recruits Mena, a member of the Ena/VASP family of actin elongation factors, which together with its phosphatase activity drive the maturation of nascent membrane protrusions into structures competent for ECM remodeling. I have established a direct interaction between SHIP2 and Met, and provide evidence to support that SHIP2 modulates Met signaling. SHIP2 plays key regulatory roles in clathrin-mediated endocytosis, cell polarity and cell motility, hence providing a rationale to investigate a role for Met-SHIP2 functional interaction in these cellular processes. Collectively, the work from this thesis identifies Met as a potent inducer of invadopodia-mediated ECM remodeling and cell invasion and identifies novel interactions involved in the regulation of the actin cytoskeleton (Gab1-cortactin, SHIP2-Mena and Met/Gab1-SHIP2). As actin cytoskeletal dynamics play a critical role in many vital cellular processes, additional biological functions for these interactions need to be explored." --
Novel Mechanisms Of Cancer Cell Invasion
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Author : Severine Van Slambrouck
language : en
Publisher:
Release Date : 2006
Novel Mechanisms Of Cancer Cell Invasion written by Severine Van Slambrouck and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with Cellular signal transduction categories.
Mechanisms Of Cancer Metastasis
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Author : Kenneth V. Honn
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Mechanisms Of Cancer Metastasis written by Kenneth V. Honn and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
The past twenty years have witnessed significant advances in the treatment of cancer by surgery and radiation therapy. Gains with cytotoxic chemotherapy have been much more modest. Of the approximately 900,000 newly diagnosed cases of cancer each year, 50010 result in death of the patient. The primary cause of these deaths is metastasis. Although the term metastasis was first coined by Recamier in 1829, only in the past ten years have there been intensive scientific investigations into the mechanisms by which tumor cells metastasize. What has emerged is a complex process of host-tumor cell interactions which has been termed the metastatic cascade. Due to the complexity of the metastatic process, the study of metastasis is multifaceted and involves elements of such areas as differentiation, en zymology, genetics, hematology, immunology, membrane biochemistry and molecular biology. The major objectives of this book were to present the most recent advances in our understanding of how tumor cells metastasize to secondary sites by the leading experts in the biology of tumor invasion and metastasis. We hope that this book will lead to new concepts for the treatment of subclinical metastatic cancer. The chapters in this book address both the basic science of metastasis and potential clinical therapies directed toward interruption of the metastatic cascade or toward eradication of subclinical metastases. Many relevant topics have been omitted due to space considerations and thus the topics included reflect the prej udices of the editors.
Molecular Mechanisms Of Cancer
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Author : Georg F. Weber
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-09-12
Molecular Mechanisms Of Cancer written by Georg F. Weber and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-09-12 with Medical categories.
This book describes molecular processes whose deregulation is important in the formation of tumors. The material is developed from basic cell signaling pathways to their roles in the clinical manifestation of specific cancers. Topics covered include molecular events intrinsic to tumor cells (leading to growth deregulation, extended lifespan, and the ability to invade surrounding tissue), protective mechanisms that prevent transformation (including DNA repair and epigenetic regulation), tumor-host interactions (with the endocrine system, the immune system, and blood vessel formation), and the underlying molecular defects of individual cancers.
Mechanisms Of Invasion And Metastasis
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Author : Marc M. Mareel
language : en
Publisher: CRC Press
Release Date : 1991-04-23
Mechanisms Of Invasion And Metastasis written by Marc M. Mareel and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1991-04-23 with Medical categories.
This book covers important biological, immunological, and molecular information essential for understanding the rationale and results of experiments and clinical observations on cell-cell and cell substrate adhesion; hydrolytic activities, cell motility; immunological and other host elements of the host-tumor ecosystem (at different sites of the metastic process); genetic and epigenetic elements of the acquisition and the expression of invasive phenotypes. 38 tables and 60 computer-drawn figures provide comprehensive overviews, and a methodological chapter emphasizing the differences and similarities between assays and their relevance for natural situations has also been included. Clinical and experimental cancer researchers, as well as as post-graduate students interested in cancer research, will find this book to be an indispensable reference resource.
Mechanisms Of Invasion In Cancer
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Author : P. Denoix
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Mechanisms Of Invasion In Cancer written by P. Denoix and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
Cellular Mechanisms Of Tumor Cell Invasion
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Author : Alanna E. Sedgwick
language : en
Publisher:
Release Date : 2013
Cellular Mechanisms Of Tumor Cell Invasion written by Alanna E. Sedgwick and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
Chapter Analysis Of Breast Cancer Cell Invasion Using An Organotypic Culture System From Book 3d Cell Culture Methods And Protocols
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Author : Romana E. Ranftl
language : en
Publisher:
Release Date : 2017
Chapter Analysis Of Breast Cancer Cell Invasion Using An Organotypic Culture System From Book 3d Cell Culture Methods And Protocols written by Romana E. Ranftl and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Metastasis is the main cause of cancer patient mortality. Local tumor invasion is a key step in metastatic dissemination whereby cancer cells dislodge from primary tumors, migrate through the peritumoral stroma and reach the circulation. This is a highly dynamic process occurring in three dimensions that involves interactions between tumor, stromal cells, and the extracellular matrix. Here we describe the organotypic culture system and its utility to study breast cancer cell invasion induced by cancer-associated fibroblasts. This is a three-dimensional model that reproduces the biochemical and physiological properties of real tissue and allows for investigating the molecular and cellular mechanisms involving tumor and its microenvironment, and their contribution to cancer cell invasion. This system provides a robust, accurate, and reproducible method for measuring cancer cell invasion and represents a valuable tool to improve the mechanistic understanding of the initial steps in metastasis.
Basement Membrane Invasion During Breast Cancer
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Author : Julie Chang
language : en
Publisher:
Release Date : 2022
Basement Membrane Invasion During Breast Cancer written by Julie Chang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with categories.
In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix (ECM) underlying epithelial and endothelial tissues, is primarily composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. Bm invasion has been thought to require protease degradation since cells, which are typically on the order of 10um in size, are too large to squeeze through the nanometer-scale pores of the BM. However, recent studies point toward a more complex picture, with physical forces generated by cancer cells facilitating protease-independent BM invasion. In this dissertation, I present work studying the impact of ECM mechanics on cancer cell invasion of the BM during breast cancer progression. Specifically, I will present work investigating the impact of ECM stiffness on the ability of cancer cells to form invadopodia protrusions in three-dimensional (3D) BM-like matrices. We show that increased stiffness of BM-like matrices diminishes invadopodia protrusion formation and cancer cell migration, contrasting the results from traditional 2D culture studies. Additionally, I will discuss my work on the development of a 3D in vitro model of collective invasion through endogenously produced BM. We find that cells utilize both proteases and forces to invade through the BM collectively. We also show that cells rely on volume expansion and contractility to exert pulling forces on the BM during invasion. These results reveal new mechanisms underlying breast cancer invasion and may lead to new strategies to inhibiting BM invasion. Ultimately, a comprehensive understanding of the diverse modes of BM invasion may yield new strategies for blocking cancer progression and metastasis.
