Project Title: PAK family kinases in pancreatic cancer – a study of therapeutic potential
Research Aims – Pancreatic cancer cells undergo a series of changes that lead them to initially multiply uncontrollably, then break away from the original tumour and move around the body spreading to other tissues. This process is called metastasis. Understanding how metastasis works may lead to the development of new drugs which could slow down or prevent the spread of disease.
Metastasis requires reorganisation of the actin cytoskeleton; processes mediated by proteins belonging to the Rho family GTPases; Rho, Rac, and Cdc42. There is considerable evidence that Rac/Cdc42interacting proteins, the p-21 activated kinase family (PAK1-6), may play a key role in cell migration and regulation of cell growth and cell survival.
Our work has already identified PAK family member PAK4 as a key regulator of prostate cancer cell movement and others have found that PAKs are important in breast cancer progression. Recently, increased levels of PAK4 protein have been found in three separate studies of pancreatic cancer and initial observations suggest that PAK4 may be a key regulator of pancreatic cancer metastasis. However, little else is know about the expression and activity of PAK family members in pancreatic cancer.
In this study we will investigate which PAKs are expressed in pancreatic cancer, and whether PAK family proteins regulate metastasis and/or cell survival in pancreatic cancer cells.
PAKs are protein kinases and their 3-dimensional structure facilitates drug development. This work will help to determine whether we should develop drugs that target PAKs in pancreatic cancer.