Role of receptor for advanced glycation end products in the complication and progression of various types of cancers.

BACKGROUND

Receptor for advanced glycation end-products popularly known as RAGE is a cell surface immunoglobulin class of molecule, binds with multiple ligands and therefore considered as a multi-ligand receptor. Use of RAGE deficient mice (RAGE(-/-)) as well as established mouse models pertaining to inflammation-associated carcinogenesis such as that of chemically induced carcinogenesis and colitis associated cancer provides a direct genetic evidence for a likelihood novel role of RAGE in cancer, with respect to its ability to lead cancer cell proliferation and survival. Besides inflammation, interaction of RAGE with its various ligands enhances oxidative stress both in cancerous and noncancerous cells which further complicates the progression of cancers.

SCOPE OF REVIEW

Till date, no single review article has discussed the mechanism of RAGE dependent complication of cancers, particularly the role of RAGE in cancer cell proliferation, angiogenesis, survival and anti-apoptosis needs to be discussed.

MAJOR CONCLUSION

RAGE enhances the number of cancer cells by activating the cell cycle proteins (e.g., cyclin D1), anti-apoptotic proteins (e.g., BCl2), prosurvival (AKT) and autophagic proteins. Role of RAGE has also been detected in formation of new blood vessels (angiogenesis) in the cancer cells and activation of myeloid derived suppressor cells (MDSCs).

GENERAL SIGNIFICANCE

This review article describes the role of RAGE in the complication of various types of cancers and the possible usefulness of RAGE dependent therapy to confront cancers in a stronger magnitude.