Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to Isoform-Specific Phosphoinositide 3-Kinase Inhibitors

International Journal of Molecular Sciences

Kira Boehm¹  CatherineA. Harwood¹  Mariam El Hasnaouy¹  Yanshuang Lyu¹  Suheyla Celik¹  Tania Maffucci¹  AmnahN. Mirza¹  Andreas Kaffa¹  Tasnim Ali¹  Viviana Mannella¹  Daniele Bergamaschi¹  Donya Kafaei Golahmadi¹  IreneM. Leigh² 

[1] Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK;Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK;

关键词: cutaneous squamous cell carcinoma;    phosphoinositide 3-kinases;    mTOR;    isoform-specific PI3K inhibitors;    BYL719;   

DOI  :  10.3390/ijms22073567

来源: DOAJ

【 摘 要 】

Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.

【 授权许可】

Unknown