cusabio2015的部落格

The protein lysyl oxidase (LOX) is an extracellular copper-dependent enzyme that functions in the crosslinking of collagens and elastin. Due to this function, LOX can remodel the tumor microenvironment. Previous research has shown that upregulation of LOX appears to promote tumor growth and metastasis and is associated with poor outcome in colon, breast, pancreas, prostate and lung cancers. (Cusabio provides LOX, EGFR, and Recombinant GGCX.)

Now researchers from the University of Manchester and The Institute of Cancer Research have identified a new pathway by which LOX uses to drive tumor progression. The have described their findings in Nature Communications. The paper “Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface” reports that LOX regulates the a transmembrane protein called epidermal growth factor receptor (EGFR). Like LOX, EGFR is also linked to tumor growth and spread.

The main goal of the study is to determine the mechanism by which LOX contributes to tumor progression. Using breast cancer cell lines, senior author Professor Richard Marais and colleagues demonstrated that LOX depletion by shRNA resulted in a reduction in the surface levels of EGFR.

In vivo experiments in mice suggested that removal of the LOX gene from cancer cells could significantly reduce the tumor volume as well as metastases. These mice lived much longer than the control mice. Overall, the findings indicate that LOX might be a therapeutic target for cancer.

To test this hypothesis, the researchers designed a complementary compound called CCT365623, which is much more potent than a common LOX inhibitor known as BAPN. Importantly, this compound can be taken orally, and it is well tolerated. The researchers administered CCT365623 to mice with spontaneous breast cancer, and found that the compound inhibited primary tumor growth and metastatic lung burden. Further investigation showed that CCT365623 led to a loss of EGFR on cell membranes in both primary and metastatic tumors.

In summary, the study reveals a molecular function of LOX in regulating EGFR and highlights the therapeutic potential of the LOX inhibitor CCT365623 in breast cancer. Since LOX is also implicated in several other cancers, the findings could have broad applications. Now CCT365623 and its analogues are being developed for LOX-driven cancers.