Highlights of This Issue

Abstract

A feature of prostate cancer is the reprogramming of lipid metabolism, but the mechanism that leads to such metabolic reprogramming is currently unknown. In the current study, Audet-Walsh and colleagues show that the androgen receptor (AR) along with the nuclear fraction of mTOR promote the activation of the sterol regulatory element-binding transcription factor 1 (SREBF1). Acting downstream of the nuclear AR/mTOR axis, SREBF1 is essential for the reprogramming of lipid metabolism. By controlling the balance between usage of citrate for mitochondrial ATP synthesis and de novo lipid synthesis, SREBF1 controls two key metabolic processes in prostate cancer.Loss of miR-489 predicts aggressive breast cancers and promotes resistance to chemotherapy. Here, autophagy was identified as an underlying mechanism responsible for resistance and miR-489-induced autophagosome accumulation was shown to be critical for its tumor-suppressive effect. In addition, miR-489 sensitized cells to doxorubicin by inhibiting doxorubicin-induced cytoprotective autophagy. These data raise the possibility that blocking late-stage autophagy may be more beneficial in sensitizing cells to doxorubicin than blocking early-stage. Importantly, clinical analysis revealed that miR-489 expression predicts overall survival in 8q22-amplified breast cancers where it may be a potential prognostic marker or therapeutic sensitizer.Since Sutton-Boveri's chromosome theory there has been insufficient progress made in understanding the molecular mechanism by which centrosome anomalies promote cancer. Remo and colleagues demonstrate that a lethal form of rhabdoid tumor arising in the colon is caused by a truncating mutation in the rootletin (CROCC) gene that encodes a fundamental component of centrosome cohesion apparatus. Importantly, genetic deletion of CROCC impaired bipolar spindle architecture leading to the generation of tetraploid cells and organelles misposition. The study describes a previously unknown link between centrosome cohesion defects and tetraploid segregation errors revealing genetic vulnerabilities of lethal tumors for which no therapeutic options are available.Despite the strong epidemiological link between hepatocellular carcinoma (HCC) and chronic hepatitis B, C and D, the molecular mechanism whereby hepatitis viruses promote liver cancer remains unknown. In particular, there is limited data on HCC associated with HDV, a small defective RNA virus that depends on HBV for assembly and transmission. Transcriptomic analysis of liver specimens, by Diaz and colleagues, demonstrated that HDV-associated HCC, unlike HCC of other viral etiologies, is characterized by an enrichment of genes involved in DNA damage and repair. Thus, this study suggests that despite the vital link of HDV with HBV, these two viruses promote liver cancer by distinct mechanisms, and provide new insights into HDV-associated HCC.