Role of p38gamma-delta in liver cancer

HCC is the most aggressive liver tumour, one of the most frequent human cancers and the third leading cause of cancer death worldwide. The reasons for its high mortality and poor prognosis are the absence of successful treatments. To date, surgical hepatectomy and Sorafenib (a general kinase inhibitor) are the only clinical options. Thus, it is extremely critical to investigate the molecular basis underlying HCC development in order to describe new molecular pathways, which are also targetable, and provide alternative and successful therapeutic options.

p38 MAPK subfamily (p38α, p38β, p38γ and p38δ) are important signaling components that transduce external stimuli into a wide range of cellular responses. Due to these essential roles, deregulated MAPKs are often found to contribute to the development of many cancers, including HCC. Lately, studies have focused on the role of p38α and p38β in HCC development. However, less is known regarding the role played by p38γ and p38δ in liver tumour initiation and development.

Here, we propose to investigate the role of p38γ and p38δ in liver physiology and liver cancer. To that end, in Sabio's lab has been generated p38γ and p38δ liver coditional Knock-Out (KO) mouse models (Alb-CRE p38γflox/flox and Abl-CRE p38δflox/flox). These mouse models are the perfect platform to study the role of p38γ and p38δ in normal liver and in liver carcinogenesis to deeply understand the molecular basis of their underlying role. Further, the silencing of p38γ and p38δ in different HCC cell lines will allow us to address the potential theraupeutic role of the inhibition of both alleles in HCC treatment. All together will lead us to a whole comprehension of the role of p38γ and p38δ in liver tumour to further find molecules to treat and beat liver cancer.