A metabolic pathway can promote cancer metastasis
According to an article published in the Journal of Cell Biology, a certain metabolic pathway in breast cancer patients will promote cancer progression after being positively adjusted, and this role is achieved the activation of cell signaling proteins Arf6. The article is entitled “P53 and metastasis and drug resistance of malignant tumor cancer caused by mevalonate pathway is achieved through Arf6” and Ari Hashimoto and colleagues are authors. It has been published in advance in online edition of journal. The article noted that the levels of some tumors expressing Arf6 signaling proteins in some patients with breast cancer are relatively high.
Mevalonate pathway (MVP) can produce a wide variety of structural units of biological molecules, from cholesterol to the fixing of certain proteins in the cell membrane of the long-chain lipid group. The p53 tumor suppressor gene mutations can increase MVP, this phenomenon will strengthen the invasiveness of some but not all breast cancer cell lines. Department of Medicine, Hokkaido University Research Division Hisataka Sabe team led by activating Arf6 suspected MVP signaling pathway enhanced invasion force, which would be more flexible to the state of over-enhanced cancer cell invasion and metastasis by promoting cell.
Ari Hashimoto and colleagues found that MVP will promote complementary Arf6 to the plasma membrane, the membrane can be Arf6 receptor tyrosine kinase activation. This path will produce the Rab11b protein fixed on the cell membrane lipid groups, Rab11b Arf6 it can be transported to the activation site developed. Rab11b transplantation can reduce the invasiveness MDA-MB-231 breast cancer cell lines; the cancer cell lines express more Arf6 signaling proteins.
Arf6 pathway may also promote breast cancer cell resistance, Hashimoto et al also found to inhibit Rab11b or Arf6 a component EPB41L5 will increase the sensitivity of MDA-MB-231 cells to two different cell toxins.
Statins can inhibit the activity of HMG-CoA reductase, while this enzyme is the key composition of the MVP. Statins were originally developed to lower cholesterol levels, but the role of statins as potential anti-cancer drugs, but the results obtained so far in clinical trials are not consistent. Hashimoto et al data suggest future research can focus Arf6 signaling protein overexpression in breast cancer patients; these patients may be able to reduce the viability of Rab11b drug sensitivity. In fact, researchers found that simvastatin can improve the sensitivity of MDA-MB-231 cells to the drug, mice were injected may also inhibit the activity of cell metastasis. Sabe said that blocking MVP may effectively kill cancer cells Arf6 passage overexpression, especially when used in combination with other drugs. Research and development of this treatment is very important, because the researchers found that the long-term survival rate is very low with the overexpression of MVP component and Arf6 signaling protein.