AsianScientist (Jan. 2, 2018) – A team of researchers at Hokkaido University, Japan, has identified a cellular protein that stabilizes tumor-promoting signals in prostate cancer cells. They published their findings in the Journal of Biological Chemistry.
The epidermal growth factor receptor (EGFR) is found on the surface of cells and is involved in cell proliferation and the development of tissues such as the lung and the digestive tract. In cancer, a mutation in the gene coding for EGFR results in its overactivation, which drives tumor formation. The drug Gefitinib is used to treat breast, lung and other cancers by inhibiting EGFR signaling, but it has only a limited effect on prostate cancer.
In this study, a group of scientists led by Professor Tadashi Matsuda of Hokkaido University, Japan, studied human prostate cancer cells to determine if there is a mechanism that potentiates EGFR signaling to promote tumor growth. They found that when EGFR is attached to a small protein called ubiquitin, it is given ‘the kiss of death’ and is tagged for degradation inside the cell. This tagging process is facilitated by a protein called c-CBL. The degradation of EGFR leads to less signaling from the receptor and reduced cell proliferation.
However, the researchers observed that a protein known as signal-transducing adaptor protein-2 (STAP-2) stabilizes EGFR by inhibiting its c-CBL-mediated ubiquitination. Furthermore, when the team suppressed STAP-2, the prostate cancer cells showed reduced proliferation and did not form a tumor when transplanted into mice.
“STAP-2 inhibitors could play a role in treating Gefitinib-resistant prostate cancers. Further studies on STAP-2 will provide new insights into cancer physiology and support the development of anticancer therapies,” said Matsuda.
The study was published in the Journal of Biological Chemistry.
The article can be found at: Kitai et al. (2017) STAP-2 Protein Promotes Prostate Cancer Growth by Enhancing Epidermal Growth Factor Receptor Stabilization.
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Source: Hokkaido University; Photo: Shutterstock.
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