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Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to
Viviana Mannella1, Kira Boehm1, Suheyla Celik1
1Centre 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.
Abstract:
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.
Insights
Targeting phosphoinositide 3-kinases (PI3Ks) shows promise for cutaneous squamous cell carcinoma (cSCC) treatment. Selective inhibition of the p110α isoform impacts cSCC cell growth and viability, suggesting a potential targeted therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with limited treatment options for metastatic cases.
- The phosphoinositide 3-kinases (PI3Ks)/Akt pathway is implicated in cSCC development and progression.
- Understanding the role of specific PI3K isoforms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic potential of isoform-specific PI3K inhibitors in cSCC.
- To determine the sensitivity of patient-derived cSCC cell lines to different PI3K inhibitors.
- To explore the role of PI3K isoforms in cSCC cell growth and viability.
Main Methods:
- Testing four patient-derived cSCC cell lines and immortalized keratinocyte cell lines.
- Utilizing isoform-specific PI3K inhibitors and pan PI3K inhibitors.
- Assessing cell growth, viability, and Akt phosphorylation levels.
Main Results:
- Pan PI3K inhibition reduced growth/viability in all tested cell lines.
- Selective inhibition of the p110α isoform decreased growth/viability in keratinocytes and two cSCC lines.
- p110α inhibition reduced Akt phosphorylation in all cSCC cell lines, indicating pathway engagement.
- cSCC cells exhibited differential sensitivity to isoform-specific PI3K inhibitors.
Conclusions:
- The PI3K/Akt pathway is critical for cSCC cell growth and viability.
- The p110α isoform is a key mediator in a subset of cSCCs.
- Isoform-specific PI3K inhibition, particularly targeting p110α, represents a potential targeted therapeutic strategy for cSCC.
