Articles in 2022

Low-molecular-weight cyclin E (LMW-E) overexpression promotes genomic instability in human mammary epithelial cells and associates with genomic instability in early-stage breast tumors. Full-length cyclin E (FL-cycE) overexpression leads to accumulation of replication stress, DNA damage, and ultimately cell death. Mechanistically, LMW-E upregulates the expression of CDC6, RAD51, and C17orf53. LMW-E, but not FL-cycE, facilitates replication stress tolerance by promoting pre-replication complex assembly in a CDC6 dependent manner and DNA damage repair in a RAD51- and C17orf53-dependent manner. Targeting the ATR-CHK1-RAD51 pathway with small molecule inhibitors significantly decreased LMW-E–overexpressing cell viability. In breast tumor samples, positive LMW-E status independently predicts genomic instability and tumor recurrence.

Graphical representation of the regulation of c-myc by the cholesterol-RORα/γ axis. Cholesterol in CRC cells is derived from de novo synthesis and exogenous uptake of LDL. Cholesterol and its derivatives inhibit the transcriptional activity of RORα/γ on NEDD4, which results in the stabilization of the c-myc protein. The combination of atorvastatin and SR1078 has a synergistic inhibitory effect on CRC cells.