The role of JNK signalling in pancreatic cancer

  • Chenxi Guo

    Student thesis: Master of Philosophy


    There is preliminary data in the lab demonstrating that the c-Jun N-terminal kinase (JNK) signalling acts as a tumour suppressor in a murine model of KRasG12D driven pancreatic cancer. Like the other mitogen-activated protein kinases (MAPKs), JNK is activated upon phosphorylation by dual specificity MAPK kinases (MKKs), namely MKK4 and MKK7. Importantly, mutational inactivation of MKK4, MKK7 and JNK frequently occurs in human pancreatic cancer genomes. Based on these findings, the aim of my project was to determine the cellular basis underlying the cooperative interaction between JNK signalling and oncogenic KRas by analysing the phenotypic consequences of over-expressing MKK4 or MKK7 in human pancreatic cancer cells. Panc-1 cells which harbour KRasG12D, P53273H and CDKN2AHD mutations, and Capan-2 cells which display only a KRasG12V mutant, were employed in my initial experiments. I found that a high level of ectopic expression of MKK7 increased JNK phosphorylation in Panc-1 cells. I confirmed that, unlike Capan-2, Panc-1 cells were not able to form acini in three-dimensional culture. Moreover, the size and number of clusters formed by Panc-1 cells decreased upon stable expression of MKK4 or MKK7. Consistently, Panc-1 over-expressing MKK4 or MKK7 displayed decreased cell proliferation and survival in two-dimensional cultures. Based on these findings, I suggest that JNK signalling may exert its tumour suppressive function in pancreatic cancer by increasing cancer cell death. Additional experiments will need to be performed to further analyse the precise function of JNK signalling in acini formation in the context of oncogenic KRas mutation.
    Date of Award1 Aug 2016
    Original languageEnglish
    Awarding Institution
    • The University of Manchester
    SupervisorPaul Shore (Supervisor) & Cathy Tournier (Supervisor)


    • signalling, JNK, MKK4, MKK7, pancreatic cancer
    • MAP kinase, three-dimensional culture

    Cite this