Functional Implications of Leucyl-tRNA Synthetase in Colorectal Cancer

Abstract

Colorectal cancer is one of challenging cancers that has high incidence rate and death rate at the same time [1]. However, since the effective targets and chemotherapeutic agents used in clinic are lack, it is necessary to identify the new drug target for controlling colorectal cancer. Here we found that leucyl-tRNA synthetase (LRS), known as a leucine sensor of mTOR signaling, is highly expressed in colorectal cancer patient tissues as well as diverse colorectal cancer cell lines [2, 3]. LRS expression significantly promotes cancer cell growth and proliferation as determined by immunoblotting, immunohistochemistry, [35S] Met incorporation, anchorage independent growth, and xenograft assay. In addition, LRS expression is positively correlated with phosphorylation of S6Kinase which is a downstream effector of mTOR. Silencing of LRS attenuates the phosphorylation of S6K, oncogenic growth, tumor mass while increase of LRS expression enhances tumorigenic propensity. Therefore, the regulation of mTOR-S6kinase pathway via suppression of LRS expression is effective way to control cancer cell growth. Taken together, this is consistent with observation that LRS may be suggested as a potential therapeutic target to control colorectal cancer and that effective tools for LRS are needed further validation and study.