Cancer Cell Invasion and Metastasis
The laboratory is interested in how cancer cells are able to dissociate from the primary tumour, invade the surrounding tissue and subsequently metastasise to distal sites. Tissue invasion and migration require cancer cells to reorganise their actin cytoskeleton as well as adhere to and degrade the surrounding extracellular matrix. It is well established that cytoskeletal rearrangement, cell adhesion formation and turnover is regulated by Rho GTPases, Rho, Rac and Cdc42. PAKs are serine/threonine kinases that operate downstream of Rho GTPases to control cytoskeletal organisation and substratum adhesion.
The PAK family can be sub-divided into two groups; Group 1 PAKs (1-3) and Group 2 PAKs (4-6) based on sequence homology and members of both groups are activated by growth factor signalling pathways. We use live cell imaging, complex 3D migration assays, biochemical and molecular approaches to investigate the role of PAK family kinases in cancer cell migration, adhesion and invasion.
- Dr Claire Wells (Group Leader)
- Michaela LesJak (Research Associate)
- Nouf Babteen (PhD student)
- Mario De Piano (PhD student)
- Katerina Pipili (PhD student)
- Madeline Gale (PhD student)
- Hoyin Lam (PhD student)
- Kiruthikah Thillai (Clinical Research Fellow)
- Anna Dart (Post-Doc- now has a Post-Doc position in the MRC centre for Developmental Neurobiology)
- Helen King (PhD Student) - Post doc position at UCL
- Fahim Ismail (PhD student) - returned to clinical duties
- Nicole Taylor (PhD Student graduated 2014 – Post-Doc position in Haemato-Oncology at KCL)
- Sally Fram (PhD Student graduated - Regulatory affairs executive, AstraZeneca
- Nur Fariesha Md. Hashim (PhD Student graduated - Lecturer University of Putra, Malaysia)
- Laura Wisniewski (Bachelor Thesis in Wells Lab) awarded “Best Bachelor Thesis of 2013 at the Faculty of Science” from Brandenburg University of Technology Cottbus-Senftenberg – now doing a PhD
- Jennifer Mariyadas Msc. graduated 2010 - now doing a PhD
- Yashodhara Pawar Msc. graduated 2012
- Bhavika Modasia Bsc. graduated 1st class 2011 – now doing a PhD
- Paul Atherton Bsc. graduated 1st class 2012– now doing a PhD
- Fram S, King, H, Sacks DB, and Wells CM (2014). A PAK6–IQGAP1 complex promotes disassembly of cell–cell adhesions Cell. Mol. Life Sci. 71:2759-2773
- King H, Nicholas NS, Wells CM. (2014) Role of p-21-Activated Kinases in Cancer Progression. Int Rev Cell Mol Biol. 309C:347-387.
- Hashim NF, Nicholas NS, Dart AE, Kiriakidis S, Paleolog E, Wells CM (2013) Hypoxia-induced invadopodia formation: a role for b-PIX – Open Biology 3:120159.
- Whale AD, Dart A, Holt M, Jones GE, Wells CM. (2013) PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity. Oncogene. 32:2114-20.
- Dart AE, Wells CM.(2013) P21-activated kinase 4 - Not just one of the PAK. Eur J Cell Biol, 92:129-38
- Whale A, Nur Hashim F, Fram S, Jones GE and Wells CM (2011) Signalling to cancer cell invasion through PAK family kinases Frontiers in Bioscience 16:849-864
- Wells CM, Whale D, Parsons M, Masters JRW and Jones GE (2010) PAK4: a pluripotent kinase that regulates prostate cancer cell adhesion. J Cell Sci. 123:1663-73
- Wells CM and Jones GE (2010). The emerging importance of group II PAKs Biochem. J. (2010) 425, 465–473
- Ahmed T, Masters JRW, Jones GE, Wells CM (2008). 'A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF’ in Cellular Signalling 7:1320-8
- Wells CM, Ahmed T, Master JRW, Jones GE (2005). 'Rho family GTPases are activated during HGF-stimulated prostate cancer cell scattering' in Cell Motility and the Cytoskeleton 62:180-94
- Wells CM, Abo A, Ridley AJ (2002) 'PAK4 is activated via PI3K in HGF-stimulated epithelial cells' in Journal of Cell Science 115:3947-56
For general enquiries, please contact:
Dr Claire Wells
Dr Claire Wells' work is supported by the Pancreatic Cancer Research Fund.