The role of circadian rhythm in breast cancer

The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus （SCN） of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer.

CHD4-induced up-regulation of ERα activity contributes to breast cancer progression

The estrogen signaling system is a crucial regulator of metabolicandphysiologicalprocesses.However,abnormal activation of estrogen signaling may play a role in breast cancer initiation and progression.Crucial to this pathway is the interaction between estrogen receptor alpha(ERa)and various co-transcription activators.1 Although numerous studies have investigated ER coregulators,the protein-protein interaction networks of ERa are not fully understood.Recent research has shown that high chromodomain helicase DNA-binding 4(CHD4)expression is linked to poor prognosis in various cancers.2,?In this study,we demonstrated that both CHD4 and ERαcontribute to breast cancer progression while providing evidence of the regulatory processes and functional interplay between these two proteins.

MZF1(Myeloid Zinc Finger 1)activates transcriptional activity of p53 and suppresses breast cancer cell proliferation via acetyltransferase PCAF(P300/CBP associated factor)

p53 is an important tumor suppressor gene.The p53 pathway is activated in response to cellular stress stimulation.However,in more than 50%of breast cancers,p53 is mutated or inactivated,which permits cancer growth.1 Although a large number of co-regulators of p53 have been identified,the integrated molecular network of p53 and the key co-factors that could transactivate p53 remain unclear.2 Myeloid Zinc Finger 1(MZF1),a member of the SCAN-ZFP(SCAN-Zinc finger protein)family,has been involved in the occurrence and development of various types of malignant tumors,including breast cancer.3 However,the exact mechanism of action remains unclear.Our study aims to investigate the cross-regulatory loop between MZF1 and p53 in breast cancer cells.