Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Seguin, Laetitia; Desgrosellier, Jay S.; Weis, Sara M.; Cheresh, David A.

doi:10.1016/j.tcb.2014.12.006

Cited by 597 publications

(578 citation statements)

References 67 publications

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“…The key roles in the process of migration and cell viability are played by transmembrane proteins called integrins. 1,2 Integrins are cell adhesion receptors on the cells' surface that bind components of the extracellular matrix (ECM), various biological ligands and receptors on adjacent cells. They are heterodimeric proteins consisting of one α-and one β-subunit.…”

Section: Introductionmentioning

confidence: 99%

“…18 different α-subunits and 8 β-subunits are known, which have been found to appear in 24 different α-β combinations, each of them possessing unique binding specificity. 2 Recent studies have exposed integrins as important factors in tumour cell survival, tumour growth and metastasis by establishing and breaking bonds between malignant cells and molecules in their surroundings. For this reason, integrins have become important targets of anti-tumour therapy.…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, integrins have become important targets of anti-tumour therapy. 2 Despite the fact that several therapeutics, integrin antagonists, have already been developed, a search for more efficient integrin-binding substances continues. [2][3][4] Snake venom (SV) proteins are broadly investigated as substances that can be used in diagnosis and treatment of human diseases.…”

Section: Introductionmentioning

confidence: 99%

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Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Latinović

Leonardi²,

Petan³

et al. 2017

ACSi

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Integrins are plasma membrane proteins, whose dysfunction frequently results in cancer pathology, and therefore they represent important targets of anti-tumour therapy. Snake venoms are a rich source of disintegrins (Dis), proteins that specifically bind integrins and thus interfere with their functions. In an attempt to discover new molecules for treatment of breast cancer, the major type of cancer in women, we isolated a dimeric Dis (Vaa-Dis) from the venom of the nosehorned viper. By cell viability testing we demonstrated that 50 nM and higher concentrations of Vaa-Dis were toxic to highly invasive human breast adenocarcinoma cell line MDA-MB-231. Wound-healing assay revealed that already at one order of magnitude lower concentrations Vaa-Dis efficiently inhibited MDA-MB-231 cell migration. This exposed a promising anti-metastatic potential of Vaa-Dis and a good perspective of these natural snake venom proteins for further research and development towards the application in breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Latinović

Leonardi²,

Petan³

et al. 2017

ACSi

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show abstract

“…Integrins are a family of adhesion receptors for extracellular matrix (ECM) proteins, integrins can transduce biochemical signals into the cell to regulate a variety of cellular functions, including proliferation, migration, survival, and drug resistance (34)(35)(36)(37). Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that mediates integrin signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Activity and Acquired Resistance Mechanism of Dovitinib (TKI258) in RET-Rearranged Lung Adenocarcinoma

Kang

Jang

Sohn

et al. 2015

Molecular Cancer Therapeutics

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RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore antitumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell-cycle arrest at G 0 -G 1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong antitumor effect of dovitinib was observed in an LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene-set enrichment analysis of gene expression and phosphor-kinase revealed that Src, a central gene in focal adhesion, was activated in LC-2/ad DR cells. Saracatinib, an src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src.

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“…Together with signals arising from receptors for soluble growth factors, integrins determine the biological activity of a cell in a given context, and thus play an important role in many (Seguin et al 2015). Therefore, on the one hand, the PEGDA hydrogel surface roughness changed significantly due to the high concentration of PS as shown in Figs.…”

Section: Effect Of Ps On Mechanical Properties Of Hydrogelsmentioning

confidence: 99%

Facile modulation of cell adhesion to a poly(ethylene glycol) diacrylate film with incorporation of polystyrene nano-spheres

Wang

et al. 2016

Biomed Microdevices

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Poly(ethylene glycol) diacrylate (PEGDA) is a common hydrogel that has been actively investigated for various tissue engineering applications owing to its biocompatibility and excellent mechanical properties. However, the native PEGDA films are known for their bio-inertness which can hinder cell adhesion, thereby limiting their applications in tissue engineering and biomedicine. Recently, nano composite technology has become a particularly hot topic, and has led to the development of new methods for delivering desired properties to nanomaterials. In this study, we added polystyrene nanospheres (PS) into a PEGDA solution to synthesize a nanocomposite film and evaluated its characteristics. The experimental results showed that addition of the nanospheres to the PEGDA film not only resulted in modification of the mechanical properties and surface morphology but further improved the adhesion of cells on the film. The tensile modulus showed clear dependence on the addition of PS, which enhanced the mechanical properties of the PEGDA-PS film. We attribute the high stiffness of the hybrid hydrogel to the formation of additional cross-links between polymeric chains and the nanosphere surface in the network. The effect of PS on cell adhesion and proliferation was evaluated in L929 mouse fibroblast cells that were seeded on the surface of various PEGDA-PS films.Cells density increased with a larger PS concentration, and the cells displayed a spreading morphology on the hybrid films, which promoted cell proliferation. Impressively, cellular stiffness could also be modulated simply by tuning the concentration of nano-spheres. Our results indicate that the addition of PS can effectively tailor the physical and biological properties of PEGDA as well as the mechanical properties of cells, with benefits for biomedical and biotechnological applications.

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Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Cited by 597 publications

References 67 publications

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Antitumor Activity and Acquired Resistance Mechanism of Dovitinib (TKI258) in RET-Rearranged Lung Adenocarcinoma

Facile modulation of cell adhesion to a poly(ethylene glycol) diacrylate film with incorporation of polystyrene nano-spheres

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