A recent study published in CLINICAL CANCER RESEARCH suggests that the protein hVps37A suppresses tumour growth in ovarian cancer. The work, which was funded by the Austrian Science Fund FWF, shows, for the first time, that this protein is significantly reduced in ovarian cancer cells.
The scientists also found that this reduction affects a cellular signalling pathway that is associated with the membrane receptor EGFR (Epidermal Growth Factor Receptor). The receptor is considered an important biological marker for the course of the disease and therapy, and also serves as a target for modern treatment of different cancer types. In fact, the cells in which hVps37A synthesis was reduced showed resistance to Cetuximab, an approved substance for inhibition of EGFR activity.
The hVps37A gene as such is not unknown to scientists. In the period 2004 to 2007, a systematic genome search as part of a project funded by the Austrian Science Fund FWF determined that, among others, this gene is down-regulated in ovarian cancer. The then head of studies, Prof. Michael Krainer, has now studied the function of this gene further in this particular type of cancer. The published results of this follow-up project show that hVps37A is a hitherto unknown tumour suppressor gene.
The Epidermal Growth Factor Receptor (EGFR) "transmits" signals from the extracellular domain to within the cell. The binding of signal substances on the cell surface of the receptor causes a chemical modification (phosphorylation) of the receptor structure on the side of the cell lumen. This signal subsequently affects numerous cellular processes significantly, including cell proliferation, and may therefore contribute to the development of cancer.EFFECTIVE DEGRADATION
This theory would explain another result found by Prof. Krainer´s group, namely that cancer cells with reduced hVps37A activity become resistant to Cetuximab, but not to Lapatinib. Cetuximab inhibits EGFR-mediated signal transduction; however, the Cetuximab-EGFR complex must then be degraded in order for the therapy to remain effective. In the case of Lapatinib, which directly inhibits EGFR phosphorylation, this is not necessary.
On the whole, the results from this FWF project offer the first fundamental description of a previously unknown tumour suppressor gene in ovarian cancer cells. Its effect on the EGF receptor also makes the tumour suppressor gene relevant for other types of cancer.
Original Publication: hVps37A Status Affects Prognosis and Cetuximab Sensitivity in Ovarian Cancer. M. Wittinger, P. Vanhara, A. El-Gazzar, B. Savarese-Brenner, D. Pils, M. Anees, T. W. Grunt, M. Sibilia, M. Holcmann, R. Horvat, M. Schemper, R. Zeillinger, C. Schöfer, H. Dolznig, P. Horak and M. Krainer. Clinical Cancer Research 2011;17:7816-7827 DOI:10.1158/1078-0432.CCR-11-0408Picture and text available from Monday, 13 February 2012, 9 am CET at:
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