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

被引：6

作者：

Mannella, Viviana ^{[1
]}

Boehm, Kira ^{[1
]}

Celik, Suheyla ^{[1
]}

Ali, Tasnim ^{[1
]}

Mirza, Amnah N. ^{[1
]}

El Hasnaouy, Mariam ^{[1
]}

Kaffa, Andreas ^{[1
]}

Lyu, Yanshuang ^{[1
,2
]}

Kafaei Golahmadi, Donya ^{[1
]}

Leigh, Irene M. ^{[3
]}

Bergamaschi, Daniele ^{[1
]}

Harwood, Catherine A. ^{[1
]}

Maffucci, Tania ^{[1
]}

机构：

[1] Queen Mary Univ London, Ctr Cell Biol & Cutaneous Res, Blizard Inst, Barts & London Sch Med & Dent, London E1 2AT, England

[2] Nanchang Univ, Sch Queen Mary, Dept Clin Med, Nanchang 330006, Jiangxi, Peoples R China

[3] Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Dent, London E1 2AD, England

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 07期

关键词：

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

D O I：

10.3390/ijms22073567

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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 p110 alpha reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110 alpha 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.

引用

页数：22