Cancer Biology

eLife assessment

This paper investigates how isoform II of transcription factor RUNX2 promotes cell survival and proliferation in oral squamous cell carcinoma cell lines. The authors used gain and loss of function techniques to provide incomplete evidence showing that RUNX2 isoform silencing led to cell death via several mechanisms including ferroptosis that was partially suppressed through RUNX2 regulation of PRDX2 expression. The study provides useful insight into the underlying mechanism by which RUNX2 acts in oral squamous cell carcinoma, but the conclusions of the authors should be revised to acknowledge that ferroptosis is not the only cause of cell death.

eLife assessment

This study provides compelling data regarding the molecular characterization of a rare tumor type with few treatment options. This fundamental work significantly advances our mechanistic understanding of solitary fibrous tumours, a critical first step towards targeted precision medicine approaches. The results of this study will be of broad interest to cancer biologists and experimental oncologists.

eLife assessment

Glioblastoma is one of the most aggressive cancers without a cure. Glioblastoma cells are known to have high mitochondrial potential. This useful study demonstrates the critical role of the ribosome-associated quality control (RQC) pathway in regulating mitochondrial membrane potential and glioblastoma growth. Some assays are incomplete; further revision will improve the significance of this study.

eLife assessment

This study provides a valuable strategy for treating mouse cutaneous squamous cell carcinoma (mCSCC) with serum derived from mCSCC-exposed mice. The exploration of serum-derived antibodies as a potential therapy for curing cancer is particularly promising but the study provides incomplete evidence for specific effects of mCSCC-binding serum antibodies. This study will be of interest to scientists seeking a novel immunotherapeutic strategy in cancer therapy.

eLife assessment

This study presents a valuable description of the cellular and transcriptional landscape of the tumor microenvironment in 27 gastric cancer (GC) patients based on their H. pylori status (HpGC, ex-HpGC, non-HpGC). The single-cell RNA sequencing dataset and computational analysis are convincing and provide a starting point that is of value for understanding H pylori-associated GC cell type composition, cell transitions, and mechanisms of response to therapy. The section correlating immunotherapy outcomes with GC cell type compositions from bulk RNAseq would have been strengthened by further comparing H. pylori GC versus non H. pylori GC.

eLife assessment

The author demonstrates that deficiency or pharmacological inhibition of O-glcNac transferase (OGT) enhances tumor immunity in colorectal cancer models. This useful study unveils that OGT deficiency triggers a DNA damage response that can affect immune status in colorectal cancers. It provides convincing evidence showing that OGT-mediated processing of HSF1 is crucial in maintaining genomic integrity.

eLife assessment

This study presents a valuable strategy to co-deliver peptides and adjuvants to antigen-presenting cells by engineering the Virus-like particle (VLP). The evidence supporting the claims of the authors is convincing, but the antitumour efficacy is unimpressive and would benefit from more antitumor experiments. The work will be of broad interest to bioengineers and medical biologists focusing on cancer vaccines.

eLife assessment

This important study using engineered mouse models provides a first and compelling demonstration of a pathogenic phenotype associated with lack of expression of p53AS, an isoform of the p53 protein with a different C-terminus than canonical p53. The role of this isoform has been elusive so far and this first demonstration represents a substantial advance in our understanding of the complex role(s) of p53 isoforms. The revised manuscript adequately addresses previous concerns.

eLife assessment

To test if somatic mutations in cancer genomes are enriched with mutations in polyadenylation signal regions, the authors observed an increased enrichment of somatic mutations that may affect the function of polyA signals and confirmed that these mutations may influence gene expression through a minigene expression experiment. This important study advances our understanding of noncoding somatic mutations by identifying a novel class of mutations that affect 3'UTR polyadenylation signals enriched in tumor suppressor genes in cancer. The evidence supporting the conclusions is convincing, with rigorous statistical analyses and experimental validation.

eLife assessment

This work describes a convincingly validated non-invasive tool for in vivo metabolic phenotyping of aggressive brain tumors in mice brains. The analysis provides a valuable technique that tackles the unmet need for patient stratification and hence for early assessment of therapeutic efficacy. However, wider clinical applicability of the findings can be attained by expanding the work to include more diverse tumor models.