A STAT3-STING-IFN axis controls the metastatic spread of small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by a high metastatic potential with an overall survival rate of ~5%. The transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed by >50% of tumors, including SCLC, but its role in SCLC development and metastasis is unclear. Here, we show that, while STAT3 deletion restricts primary tumor growth, it paradoxically enhances metastatic spread by promoting immune evasion.

Mapping the IMiD-dependent cereblon interactome using BioID-proximity labelling.

Immunomodulatory imide drugs (IMiDs) are central components of therapy for multiple myeloma (MM). IMiDs bind cereblon (CRBN), an adaptor for the CUL4-DDB1-RBX1 E3 ligase to change its substrate specificity and induce degradation of 'neosubstrate' transcription factors that are essential to MM cells. Mechanistic studies to date have largely focussed on mediators of therapeutic activity and insight into clinical IMiD toxicities is less developed.

Practices Supporting Community Recovery and Healing from Climate-Related Disasters: A Systematic Review.

This systematic review investigated the practices that support and hinder the recovery and healing of communities and the environments within which they live, following climate-related environmental disasters. Although the literature focused on recovery is dominated by interventions aimed at the individual and their mental health, a thematic analysis of thirty-six studies established a range of practices that enhance collective recovery and healing. Four narratives were identified from the findings highlighting key practices: (1) collective and community-led recovery; (2) recognising the criticality of context, place, and identity; (3) adopting a holistic conception of well-being and Country-centred practices; and (4) decolonising and Indigenising the literature.

Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.

TP53 and RB1 loss-of-function mutations are common in osteosarcoma. During development, combined loss of TP53 and RB1 function leads to downregulation of autophagy and the aberrant formation of primary cilia, cellular organelles essential for the transmission of canonical Hedgehog (Hh) signaling. Excess cilia formation then leads to hypersensitivity to Hedgehog (Hh) ligand signaling.

A STAT3 protein complex required for mitochondrial mRNA stability and cancer.

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive.