Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death.

The quest for targeted therapies is critical in the battle against cancer. The RAS/MAP kinase pathway is frequently implicated in neoplasia, with ERK playing a crucial role as the most distal kinase in the RAS signaling cascade. Our previous research demonstrated that the interaction between ERK and MYD88, an adaptor protein in innate immunity, is crucial for RAS-dependent transformation and cancer cell survival.

The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context.

Nutrient availability is a key determinant of tumor cell behavior. While nutrient-rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor general control non-derepressible 2 (GCN2; also known as eIF-2-alpha kinase 4) represses the expression of the precursor of ribosomal RNA (rRNA), 47S, under metabolic stress.

Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming.

Reactive oxygen species (ROS) are considered to be the main drivers of inflammatory bowel disease. We investigated whether this permanent insult compels intestinal stem cells to develop strategies to dampen the deleterious effects of ROS. As an adverse effect, this adaptation process may increase their tolerance to oncogenic insults and facilitate their neoplastic transformation.

The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated.

The kynurenine pathway has been highlighted as a gatekeeper of immune-privileged sites through its ability to generate from tryptophan a set of immunosuppressive metabolic intermediates. It additionally constitutes an important source of cellular NAD for the organism. Hijacking of its immunosuppressive functions, as recurrently observed in multiple cancers, facilitates immune evasion and promotes tumor development.

Increased expression of the thyroid hormone nuclear receptor TRα1 characterizes intestinal tumors with high Wnt activity.

Our previous work demonstrated a key function of the thyroid hormone nuclear receptor TRα1, a T3-modulated transcription factor, in controlling intestinal development and homeostasis the Wnt and Notch pathways. Importantly, increased expression of TRα1 in the intestinal epithelium in a mutated genetic background (-TRα1/Apc mice) accelerated tumorigenesis and contributed to a more aggressive tumor phenotype compared to that of the mutants alone. Therefore, the aim of this study was to determine the relevance of this synergistic effect in human colorectal cancers and to gain insights into the mechanisms involved.