A Modified <em>In vitro</em> Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion

Abstract Metastasis is the main cause of cancer associated morbidity which will account for approximately 600,000 deaths in the USA in 2021. Defining new mechanisms that drive cancer metastasis is vital for developing new therapeutic strategies and improving clinical outcomes for cancer patients. Herein, we describe a recently established three-dimensional Matrigel drop invasion assay to measure cancer cell invasion and migration capability in vitro. This assay is a versatile and simple tool to test the ability of cells to invade and migrate, test the functional role of genes of interest in cell invasion and migration, analyze the localization of the target proteins at the cell invasion edge in situ, and screen drug effects on cancer cell invasion and migration.

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EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Cells ◽

10.3390/cells10020388 ◽

2021 ◽

Vol 10 (2) ◽

pp. 388

Author(s):

Brice Chanez ◽

Kevin Ostacolo ◽

Ali Badache ◽

Sylvie Thuault

Keyword(s):

Breast Cancer ◽

Cancer Cell ◽

Cell Invasion ◽

Focal Adhesions ◽

Matrix Degradation ◽

Cancer Cell Invasion ◽

Wild Type ◽

Spatial Regulation ◽

Invadopodia Formation

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

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The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.01.531 ◽

2015 ◽

Vol 137 (1) ◽

pp. 125-133 ◽

Cited By ~ 39

Author(s):

Juanni Li ◽

Long Li ◽

Zexia Li ◽

Guanghui Gong ◽

Puxiang Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cell ◽

Cell Invasion ◽

Ovarian Cancer Cell ◽

Human Ovarian Cancer ◽

Cancer Cell Invasion ◽

Human Ovarian Cancer Cell

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A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-07-2026 ◽

2008 ◽

Vol 6 (5) ◽

pp. 715-724 ◽

Cited By ~ 34

Author(s):

Xiaohua Shi ◽

Chuanyue Wu

Keyword(s):

Cancer Cell ◽

Cell Invasion ◽

Cancer Cell Invasion ◽

Inducible Gene

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The Role of WAVE2 Signaling in Cancer

Biomedicines ◽

10.3390/biomedicines9091217 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1217

Author(s):

Priyanka Shailendra Rana ◽

Akram Alkrekshi ◽

Wei Wang ◽

Vesna Markovic ◽

Khalid Sossey-Alaoui

Keyword(s):

Actin Cytoskeleton ◽

Cancer Cell ◽

Cell Invasion ◽

Critical Role ◽

Therapeutic Strategies ◽

Small Gtpases ◽

Cancer Cell Invasion ◽

Invasion And Metastasis ◽

Regulatory Complex

The Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE)—WAVE1, WAVE2 and WAVE3 regulate rapid reorganization of cortical actin filaments and have been shown to form a key link between small GTPases and the actin cytoskeleton. Upon receiving upstream signals from Rho-family GTPases, the WASP and WAVE family proteins play a significant role in polymerization of actin cytoskeleton through activation of actin-related protein 2/3 complex (Arp2/3). The Arp2/3 complex, once activated, forms actin-based membrane protrusions essential for cell migration and cancer cell invasion. Thus, by activation of Arp2/3 complex, the WAVE and WASP family proteins, as part of the WAVE regulatory complex (WRC), have been shown to play a critical role in cancer cell invasion and metastasis, drawing significant research interest over recent years. Several studies have highlighted the potential for targeting the genes encoding either part of or a complete protein from the WASP/WAVE family as therapeutic strategies for preventing the invasion and metastasis of cancer cells. WAVE2 is well documented to be associated with the pathogenesis of several human cancers, including lung, liver, pancreatic, prostate, colorectal and breast cancer, as well as other hematologic malignancies. This review focuses mainly on the role of WAVE2 in the development, invasion and metastasis of different types of cancer. This review also summarizes the molecular mechanisms that regulate the activity of WAVE2, as well as those oncogenic pathways that are regulated by WAVE2 to promote the cancer phenotype. Finally, we discuss potential therapeutic strategies that target WAVE2 or the WAVE regulatory complex, aimed at preventing or inhibiting cancer invasion and metastasis.

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MATHEMATICAL MODELLING OF CANCER CELL INVASION OF TISSUE: THE ROLE OF THE UROKINASE PLASMINOGEN ACTIVATION SYSTEM

Mathematical Models and Methods in Applied Sciences ◽

10.1142/s0218202505000947 ◽

2005 ◽

Vol 15 (11) ◽

pp. 1685-1734 ◽

Cited By ~ 169

Author(s):

M. A. J. CHAPLAIN ◽

G. LOLAS

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

The Body ◽

Plasminogen Activation ◽

Cancer Cell Invasion ◽

Plasminogen Activation System ◽

Activation System ◽

Spatio Temporal

The growth of solid tumours proceeds through two distinct phases: the avascular and the vascular phase. It is during the latter stage that the insidious process of cancer invasion of peritumoral tissue can and does take place. Vascular tumours grow rapidly allowing the cancer cells to establish a new colony in distant organs, a process that is known as metastasis. The progression from a single, primary tumour to multiple tumours in distant sites throughout the body is known as the metastatic cascade. This is a multistep process that first involves the over-expression by the cancer cells of proteolytic enzyme activity, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). uPA itself initiates the activation of an enzymatic cascade that primarily involves the activation of plasminogen and subsequently its matrix degrading protein plasmin. Degradation of the matrix then enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body. In this paper we consider a mathematical model of cancer cell invasion of tissue (extracellular matrix) which focuses on the role of the plasminogen activation system. The model consists of a system of reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, urokinase plasminogen activator (uPA), uPA inhibitors, plasmin and the host tissue. The focus of the modelling is on the spatio-temporal dynamics of the uPA system and how this influences the migratory properties of the cancer cells through random motility, chemotaxis and haptotaxis. The results obtained from numerical computations carried out on the model equations produce rich, dynamic heterogeneous spatio-temporal solutions and demonstrate the ability of rather simple models to produce complicated dynamics, all of which are associated with tumour heterogeneity and cancer cell progression and invasion.

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