Professor Toshitaka Sanabe and Assistant Professor Ari Hashimoto of the Graduate School of Medicine, Hokkaido University have collaborated with Osaka University and Tohoku University to make the intracellular mevalonic acid pathway into cancer invasion / metastasis and treatment resistance. He announced that he was significantly involved and that the mevalonic acid pathway inhibitor statin was effective in treating breast cancer.

 The researchers have previously shown that the Arf6 protein and its signaling factor, AMAP1, are highly expressed in many high-grade breast cancers, promoting infiltration and metastasis.We have now found that EPB41L5, a protein originally found in mesenchymal cells, is strongly expressed in advanced malignant breast cancer, and that EPB41L5 is a binding partner for AMAP1 and is essential for infiltration metastasis. , Clarified that it is an infiltration-type signal pathway that appears in advanced-grade cancer.

 Most breast cancers activate Arf6 by aberrant expression of growth factor receptors, and we have further revealed that mevalonate pathway activity is essential for this Arf6 activation, along with molecular details.This revealed how mutations in the tumor suppressor gene TP53 are involved in the progression of breast cancer malignancy, and that the highly expressed Arf6-AMAP1-EPB41L5 pathway is the basis of drug resistance as well as infiltration metastasis. ..

 Statins used for the treatment of hyperlipidemia are inhibitors of the mevalonic acid synthesis pathway, but statins were able to significantly reduce invasive metastasis and drug resistance of breast cancer.However, this is limited to breast cancers that strongly express Arf6, AMAP1, and EPB41L5.On the other hand, analysis of the international breast cancer database also revealed that high expression of the Arf6-AMAP1-EPB41L5 pathway was strongly associated with low patient survival.

 It is explained that the results of this research are findings that will greatly contribute to the improvement of cancer treatment methods in the future, and because of their importance, they have been widely taken up by InFocus of JCB magazine.

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