Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights.

The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment.

Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity.

The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure.

MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.

MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved.

Phosphoproteome and gene expression profiling of ALK inhibition in neuroblastoma cell lines reveals conserved oncogenic pathways.

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is a clinical target of major interest in cancer. Mutations and rearrangements in trigger the activation of the encoded receptor and its downstream signaling pathways. mutations have been identified in both familial and sporadic neuroblastoma cases as well as in 30 to 40% of relapses, which makes ALK a bona fide target in neuroblastoma therapy.

Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia.

Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia.

Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events.

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways.

Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure.

Alcohol use disorder is a chronic relapsing brain disorder and a global health issue. Prolonged high alcohol consumption increases the risk for dependence development, a complex state that includes progressive alterations in brain function. The molecular mechanisms behind these changes remain to be fully disclosed, but several genes show altered expression in various regions of the rat brain even after modest alcohol exposure.

Cadmium Causes Misfolding and Aggregation of Cytosolic Proteins in Yeast.

Cadmium is a highly poisonous metal and is classified as a human carcinogen. While its toxicity is undisputed, the underlying molecular mechanisms are not fully understood. Here, we demonstrate that cadmium induces aggregation of cytosolic proteins in living cells.