Integrin Signaling in Cancer Cell Survival and Chemoresistance

Aoudjit, Fawzi; Vuori, Kristiina

doi:10.1155/2012/283181

Cited by 154 publications

(179 citation statements)

References 173 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…Confirmatory data for both issues are shown here as the tested A549 and H1299 human NSCLC cells show higher radioresistance as well as a diminished cytotoxic and radiosensitizing potential of cetuximab on adhesion to fibronectin. These findings corroborate published data in cells from other malignancies and on other drugs (41)(42)(43).…”

Section: Discussionsupporting

confidence: 92%

Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis

et al. 2013

View full text Add to dashboard Cite

Inherent and acquired resistance to targeted therapeutics continues to emerge as a major clinical obstacle. For example, resistance to EGF receptor targeting occurs commonly, more so than was expected, on the basis of preclinical work. Given emerging evidence that cancer cell-substrate interactions are important determinants of therapeutic sensitivity, we examined the impact of cell-fibronectin interactions on the efficacy of the EGF receptor antibody cetuximab, which is used widely for lung cancer treatment. Our results revealed the potential for cell-fibronectin interactions to induce radioresistance of human non-small cell lung cancer cells. Cell adhesion to fibronectin enhanced tumor cell radioresistance and attenuated the cytotoxic and radiosensitizing effects of cetuximab. Both in vitro and in vivo, we found that cetuximab treatment led to a remarkable induction of fibronectin biosynthesis. Mechanistic analyses revealed the induction was mediated by a p38-MAPK-ATF2 signaling pathway and that RNAi-mediated inhibition of fibronectin could elevate the cytotoxic and radiosensitizing potential of cetuximab. Taken together, our findings show how cell adhesion blunts cetuximab, which, by inducing fibronectin, generates a self-attenuating mechanism of drug resistance.

show abstract

Section: Discussionsupporting

confidence: 92%

Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Changes in integrin expression are associated with regulation in cell growth, differentiation and death by providing a dynamic linkage to the extracellular matrix and intracellular actin cytoskeleton (Aoudjit & Vuori, 2012). The upregulation of 4-integrin in MCF-7 cells could be due to the direct influence of the compound 1 or to the reaction of the tumorigenic cells losing detachment.…”

Section: Discussionmentioning

confidence: 99%

Novel anticancer alkene lactone fromPersea americana

Falodun¹,

Engel

Kragl³

et al. 2013

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer. Objective: To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana. Materials and methods: The MCF-7 cells were treated with different concentrations of the pure compound for 48 h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry. Results: One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10 mg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12 A cell was significantly stimulated by 10 mg/mL. The IC 50 value for MCF-7 cells is 20.48 mg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10 mg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10 mg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1 mg/mL of 1 caused a decrease of a4-, a6-, b1-and b3-integrin expression. Conclusions: The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.

show abstract

“…[8,16,18] In addition, cancer cell-derived ECM proteins (fibronectin, collagen, and laminin) protect cancer cells from chemotherapyinduced apoptosis via activation of the PI3k/AKT pathway [ Figure 1]. [72,73] Cancer cell-derived ECM proteins mediate the cancer cell-stromal cell crosstalk. Hyaluronan production by stroma fibroblasts is stimulated by factors secreted by cancer cells.…”

Section: Cancer Cell-derived Ecm In Cancer Progression and Metastasismentioning

confidence: 99%

Function of cancer cell-derived extracellular matrix in tumor progression

Xiong¹,

Xu²

2016

JCMT

118

View full text Add to dashboard Cite

How to cite this article: Xiong GF, Xu R. Function of cancer cell-derived extracellular matrix in tumor progression. J Cancer Metasta Treat 2016;2:357-64.Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment. Key words:Tumor microenvironment, extracellular matrix, cancer progression, metastasis ABSTRACT Article history:

show abstract

Integrin Signaling in Cancer Cell Survival and Chemoresistance

Cited by 154 publications

References 173 publications

Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis

Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis

Novel anticancer alkene lactone fromPersea americana

Function of cancer cell-derived extracellular matrix in tumor progression

Contact Info

Product

Resources

About