Integrin αVβ3 expression in tongue squamous carcinoma cells CAL27 confers anticancer drug resistance through loss of pSRC(Y418) (CROSBI ID 636166)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Stojanović, Nikolina ; Brozović, Anamaria ; Majhen, Dragomira ; Herak Bosnar, Maja ; Osmak, Maja ; Fritz, Gerhard ; Ambriović Ristov, Andreja
engleski
Integrin αVβ3 expression in tongue squamous carcinoma cells CAL27 confers anticancer drug resistance through loss of pSRC(Y418)
Integrins play key roles in the regulation of tumor cell adhesion, migration, invasion and sensitivity to anticancer drugs. In the present study we investigate the mechanism of resistance of tongue squamous carcinoma cells Cal27 with de novo integrin αvβ3 expression to anticancer drugs. Cal27-derived cell clones, obtained by transfection of plasmid containing integrin subunit β3 cDNA, as compared to control cells demonstrate: expression of integrin αvβ3 ; increased expression of integrin αvβ5 ; increased adhesion to fibronectin and vitronectin ; resistance to cisplatin, mitomycin C, doxorubicin and 5-fluorouracil ; increased migration and invasion, increased amount of integrin-linked kinase (ILK) and decreased amounts of non-receptor tyrosine kinase (Src) and pSrc(Y418). Knockdown of ILK and integrin β5 in cells expressing integrin αvβ3 ruled out their involvement in drug resistance. Opposite, Src knockdown in Cal27 cells which led to a reduction in pSrc(Y418), as well as treatment with the pSrc(Y418) inhibitors dasatinib and PP2, conferred resistance to all four anticancer drugs, indicating that the loss of pSrc(Y418) is responsible for the observed effect. We identified differential integrin signaling between Cal27 and integrin αvβ3-expressing cells. In Cal27 cells integrin αv heterodimers signal through pSrc(Y418) while this is not the case in integrin αvβ3-expressing cells. Finally, we show that dasatinib counteracts the effect of cisplatin in two additional head and neck squamous cell carcinoma (HNSCC) cell lines Cal33 and Detroit562. Our results suggest that pSrc(Y418) inhibitors, potential drugs for cancer therapy, may reduce therapeutic efficacy if combined with chemotherapeutics, and might not be recommended for HNSCC treatment.
integrin αvβ3 ; integrin αvβ5 ; integrin mediated drug resistance ; pSrc (Y418) ; ILK ; migration
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Podaci o prilogu
65-65.
2016.
objavljeno
Podaci o matičnoj publikaciji
40th Anniversary HDBMB2016 Book of Abstracts
Katalinić, Maja ; Kovarik, Zrinka
Zagreb:
1847-7836
Podaci o skupu
Congress of the Croatian Society of Biochemistry and Molecular Biology on the Occasion of the 40th Anniversary, HDBMB2016
poster
01.07.2016-04.07.2016
Split, Hrvatska