Cancer Biology

eLife Assessment

The article uses a cell-based model to investigate how mutations and cells spread throughout a tumour. The paper uses published data and the proposed model to understand how growth and death mechanisms lead to the observed data. This work provides an important insight into the early stages of tumour development. From the work provided here, the results are convincing, using a thorough analysis.

eLife Assessment

In this important study, the authors used a zebrafish model and scRNAseq analysis to show that a subset of keratinocytes within melanoma microenvironment highly up-regulate Twist and undergo Epithelial-Mesenchymal Transition (EMT). Surprisingly, when overexpressing Twist in keratinocytes, the resulting alteration in keratinocytes is inhibitory for melanoma invasion in both zebrafish and human cell culture models. The results are supported by overall convincing experimental data that provide new insights into the interactions between melanoma cells and their environment.

eLife Assessment

This work attempts to demonstrate an ATP-independent non-canonical role of proteasomal component PA28y in the promotion of oral squamous cell carcinoma growth, migration, and invasion. The evidence around the following two areas remains incomplete and would benefit from further experimental work: 1) the stabilisation of the complement C1q binding protein (C1QBp) by PA28y, and 2) the impact of the PA28y-C1QBp interaction on mitochondrial function.

eLife assessment

This study presents a valuable finding and developed ME3BP-7 as a novel microencapsulated formulation of 3BP, which specifically targets MCT1-overexpressing PDAC cells. It demonstrates its specificity and efficacy in vitro and in PDAC mouse models, with significant anti-tumor effects and improved serum stability. Overall, the evidence supporting the authors' claims is solid.

eLife assessment

The authors provide useful data to support the existence of a regulatory pathway starting with SPI1-driven ZFP36L1 expression, that goes on to downregulate HDAC3 expression at the transcript level, leading to PD-L1 upregulation due to implied enhanced acetylation of its promoter region. This is therefore an interesting pathway that adds to our understanding of how PD-L1 expression is controlled in gastric cancer. However, this is likely one of many possible pathways that impact PD-L1 expression, and the data are currently incomplete to support the claims made.

eLife assessment

This important study investigates the molecular mechanisms underpinning how the tumor necrosis factor alpha-induced protein, TIPE, regulates aerobic glycolysis to promote tumor growth in melanoma. Solid data using multiple independent approaches provide new insights into the molecular mechanisms underpinning aerobic glycolysis, also known as the Warburg Effect, in melanoma cells. However, further investigation of a potential oncogenic effect of TIPE in melanoma patients is warranted and more advanced metabolomic and bioenergetic assays could be employed. The work will be of interest to biomedical researchers working in cancer and metabolism.

eLife assessment

The study presents a potentially valuable approach by combining two measurements (pHLA binding and pHLA-TCR binding) to improve predictions of which mutations in colorectal cancer are likely to be presented to and recognised by the immune system. While this approach is promising, the evidence supporting the primary claim remains somewhat incomplete. The experimental validation of the computational predictions with actual immune responses is still limited, despite the increase in sample size from 4 to 8 in this revision.

eLife assessment

This work provides solid evidence that Transforming Growth Factor β Activated Kinase 1 (TAK1) regulates esophageal squamous cell carcinoma (ESCC) tumor proliferation and metastasis. The findings are valuable to the field of molecular tumor biology in general and to the understanding of ESCC tumor invasiveness and metastatic potential.

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.