Molecular and Cellular Oncology最新文献

Membraneless condensates have recently caught the attention of biologists as hubs for cellular components required for catalysis of basic processes. Whether they are real has become the center of heated discussion where the main issues are their mechanism of assembly and function. A recent study describing these condensates as hubs for protein degradation by the ubiquitin system may shed a new light on this recent development in cell biology.

Colon cancer progression is among the risks that increase with obesity. We have recently unveiled the molecular mechanism by which adipose tissue-released molecules, HGF and IL-6, make colorectal cancer (CRC) cells acquiring mesenchymal traits. Targeting of adipose-derived factors abrogate the metastatic potential of CRC stem cells (CR-CSCs) in obese patients.

The calcium-independent phospholipase iPLA2β has been identified as a transcriptional target of the tumor suppressor TP53 (or p53). Unlike GPX4 (glutathione peroxidase 4), iPLA2β is not required for normal homeostasis but critical for ferroptosis during stress responses. Our results implicate iPLA2β as an essential regulator in a noncanonical ferroptosis pathway.

The protein-lipid complex alpha1-oleate, derived from HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), is identified as a molecular entity with significant therapeutic potential. Structural characterization of the complex and results of a successful placebo-controlled clinical trial are presented.

Autophagy is a central recycling process, and it plays a complex role in cancer. We discovered that when autophagy is blocked, cancer cells compensate by increasing mitochondrial-derived vesicles. However, there are many unanswered questions remaining, particularly in the context of the dual roles of autophagy in cancer.

The identification of the Rag GTPases initiated the deciphering of the molecular puzzle of nutrient signaling to the mechanistic target of rapamycin (mTOR), and spurred interest in targeting this pathway to combat human disease. Recent mouse genetic studies have provided pathophysiological insight and pointed to potential indications for inhibitors of the Rag GTPase pathway.

Accurate chromosome segregation depends on tight regulation of the protease separase, which cleaves the ring-shaped cohesin complex that entraps the two sister chromatids. We recently reported structures of human separase bound to its inhibitors securin or the cyclin-dependent kinase 1 (CDK1)-cyclin B1 (CCNB1)-cyclin-dependent kinases regulatory subunit 1 (CKS1) complex and discovered an array of molecular mechanisms that block cohesin-cleavage.

Cells that lack attachment to the extracellular matrix (ECM) experience metabolic defects that can lead to caspase-independent cell death. Recently, we discovered that serum and glucocorticoid kinase-1 (SGK1) plays a critical role in the regulation of glucose metabolism, the promotion of energy production, and ultimately the survival of ECM-detached cells. Abbreviations: ECM, extracellular matrix; SGK1, serum and glucocorticoid kinase-1; ROS, reactive oxygen species; CCCP, cyanide m-chlorophenyl hydrazine; PPP, pentose phosphate pathway; G3P, glyceraldhyde-3-phosphate; shRNA, short hairpin RNA; TCA, tricarboxylic acid.

The inherent complexity of cancer complicates treatment. Identifying higher-order principles that govern cancer biology can circumvent this problem and pinpoint broadly applicable treatment options. We recently found that opposite expression and pro- versus anti-cancer activity of a single transcriptional complex functionally stratifies cancer into binary superclasses.

Genome instability is a hallmark of cancer. ATP-dependent chromatin remodelers are frequently altered in cancer. We have recently reported that the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protects the genome by limiting R-loop-mediated genome instability, mainly that caused by transcription-replication conflicts. Here we discuss the significance and biomedical applications of this finding.