Cancer Institute Seminar Series - Prof Jesus Gil

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, this “senescence-associated secretory phenotype” (SASP) is a potential therapeutic target. We performed an RNAi screen for genes that regulate the SASP without affecting the senescence growth arrest. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Amongst the screen candidates was PTBP1, a factor regulating alternative splicing. Knockdown of PTBP1 prevents the pro-tumorigenic effects of the SASP without interfering with growth arrest. PTBP1 regulates the alternative splicing of genes controlling intracellular trafficking, such as the exocyst component EXOC7. We found that PTBP1-mediated EXOC7 isoform switching modulates exocyst activation to regulate the SASP. Our study identifies PTBP1 and EXOC7 as new regulators of inflammation and provides functional evidence that specific regulation of the SASP represents a powerful therapy against inflammation driven cancer.

• Prof Jesus Gil academic profile

Hosted by Dr Richard Jenner
A light lunch will be served after the seminar.

This seminar has been sponsored in part by the NIHR/UCLH Biomedical Research Centre and Cancer Research UK