UCL Cancer Institute

Tumour Models in Cancer

Group Leader: Dr. Christina Gewinner

Multiple genetic changes are responsible for ovarian cancer development and progression. Our laboratory is developing novel tumour models aiding the understanding of genetic changes in the phosphatidylinositol 3-kinase (PI3K) signalling pathway that will lead to the development of new therapeutic strategies for ovarian cancer patients.


Ovarian Cancer is the fourth most common cause of cancer death in women in the UK. My laboratory focuses on the initiation and maintenance of ovarian cancer, as well as the development of novel treatment options for ovarian cancer patients.

Model of PTEN and INPP4B

Fig 1   A model indicating the roles of PTEN and INPP4B in regulation of signaling downstream of class I PI3Ks.

Frequently, tumours show loss or gain of key genetic components, such as BRCA1/2 (breast cancer 1/2), PTEN (phosphatase and tensin homolog), and PIK2CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) that lead to initiation of tumours. The phosphoinositide 3-kinase (PI3K)/AKT pathway is a key component of cell survival and is viewed to be important in many aspects of cell motility and adhesion, and hence it is able to contribute to metastatic/invasive phenotypes of various cancer cells. PI3K was reported to be involved in cell growth and transformation, and indirect or direct deregulation of PI3K signalling causes aberrant cell-cycle progression and transformation of normal cells into tumor cells. Due to hyperactivation of the PI3K/Akt pathway in many cancers and its role in multiple aspects of cancer progression, inhibition of the PI3K/Akt signalling pathway has been investigated as a treatment for cancer.

We have discovered a novel tumour suppressor in the PI3K pathway, the inositol polyphosphate 4-phosphatase type II (INPP4B). We found loss of expression of INPP4B in various cancers, in particular in breast, ovary and melanoma. Loss of INPP4B showed in in vitro assays similarities, but also important differences to loss of PTEN, a well characterized tumour suppressor in the PI3K/Akt pathway. Strikingly, we found that loss of INPP4B in ovarian cancer correlated with poor patient outcome (Gewinner C. et al., Cancer Cell, 2009).

Currently, we are developing novel INPP4B-deficient tumour models that will contribute to increased understanding of ovarian cancer and reveal new therapeutic strategies.

models of knokdown

Fig 2   Knockdown of INPP4B or PTEN in MCF-10A cells results in dysmorphic cell clusters upon growth in three-dimensional culture.


Group Members

•  Mr. Felipe Cia Viciano
•  Ms. Laura Ip, BSc



Selected Publications

S Chen*, X Jiang*, C A Gewinner*, J M Asara, N I Simon, C Cai, L C Cantley and S P Balk. "Tyrosine Kinase BMX Phosphorylates Phosphotyrosine-Primed Motif Mediating the Activation of Multiple Receptor Tyrosine Kinases ", Science Signaling, 6, ra40 (2013), pp.1-11 .
*Authors contributed equally to this work

Christina Gewinner, Zhigang C. Wang, Andrea Richardson, Lucia Rameh , and Lewis Cantley. "Evidence that Inositol poyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling", Cancer Cell 16, 1-11, August 4, 2009.

Christina Gewinner, Gerald Hart, Natasha Zachara, Robert Cole, and Bernd Groner, "The coactivator CREB binding potein (CBP) interacts preferentially with the glycosylated form of the transcription factor Stat5", JBC (2004) Vol.279 No.5 Jan30, pp.3563-3572

Mueller CW, Soler-Lopez M, Gewinner C and Groner B, "X-ray cristal structure of Stat proteins and structure activity relationship", Signal transducers and activators of transcription (STATs): Activation and Biology, PB Sehgal, DE Levy and T Hirano (eds.), Kluwer Academic Publishers (2003)




• Prof. Lewis Cantley, Harvard Medical School, Boston, USA
• Dr. Phillip Hawkins, Barbraham Institute, Cambridge, UK
• Prof Simon Gayther, Women’s Health Institute, London, UK
• Dr. Mark Lythgoe, UCL Cancer Institute, London, UK
• Dr. Roshan Agarwal, Imperial College, London, UK
• Prof. John Hartley, UCL Cancer Institute, London, UK
• Dr. Alexander Hergowic, UCL Cancer Institute, London, UK
• Dr. Robin Ketteler, LMCB-MRC, London, UK