US EPA

4533094 

Journal Article 

Kinase Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 

Cleveland, J 

2017 

This work directly addresses how breast cancers grow and how this uncontrolled cellular growth can be stopped. Specifically, we will decipher the role of the 40S ribosome assembly pathway for tumor cell growth and death induced by novel anti-tumor agents. Here we propose to further dissect the role and mechanism of the CK1delta-to-Ltv1circuit in the maintenance of the malignant state in triple negative breast cancer. In Aim 1 we will clarify if the anti-proliferative activity of CK1delta inhibitors is due to a block of Ltv1 release in ribosome assembly; if the CK1delta-to-Ltv1circuit is overactive in breast cancer cells; if bypass of the CK1delta-dependent regulation of 40S ribosome assembly augments the tumorigenic potential of cancer cells. In Aim 2 we will confirm preliminary observations that the autophagy and exosome pathways degrade stalled assembling ribosomes, leading to cell death; and test if enhancing these pathways by overexpression or administration of FDA-approved drugs that induce autophagy, potentiates the effect from CK1delta inhibitors.