CCBIO Seminar: Kalle Sipila
Welcome to CCBIO Seminar with speaker Kalle Siplia from the Centre for Stem Cells & Regenerative Medicine, King's College London. Title: Integrative genomic and functional analysis of human primary oral SCC cells.
Apart from the interesting talks, the CCBIO seminars are a good way to meet CCBIO members and associates. Please feel free to inform others about this seminar as all are welcome both to the lecture and the pizza get-together afterwards.
Invited speaker: Kalle Sipila, Centre for Stem Cells & Regenerative Medicine, King's College London, UK.
Time: June 15th 2017 at 14:30, Auditorium 4, BBB
Host: Donald Gullberg
Title: "Integrative genomic and functional analysis of human primary oral SCC cells"
Oral squamous cell carcinoma (OSCC) is heterogeneous both at the cellular and genetic levels. A panel of HPV-negative OSCC cell lines was created by the Rheinwald-Green method in order to produce an in vitro model to study the questions arising from this heterogeneity. The mutational landscapes of the lines were generated by whole exome sequencing and the results demonstrated that the spectrum of genetic lesions in cell lines is representative of primary OSCC in The Cancer Genome Atlas. Among the findings, there was loss of function and truncation mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8) that are incompletely characterized in OSCC. Decreased function of FAT1 and CASP8 in our OSCC cells led to increased cell migration and clonal growth as well as resistance to apoptosis.
High-throughput drug screening of OSCC cell lines revealed sensitivity of some cell lines to an HSP90 inhibitor that has been shown to elicit an effect by modulating the Hippo pathway. In another study performed in our lab, the hippo effector YAP was one of the most important growth regulators in squamous cell carcinoma cells. Inhibition of HSP90 reduced both growth and tumour metastasis in OSCC xenograft models.
The OSCC lines represent a useful resource for studying the impact of different mutations on cancer cell behavior. The future aim is to use this resource for linking drug sensitivity to genetic markers.