Cancer Biology

eLife Assessment

This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

eLife Assessment

This study investigates low-affinity Ca2+ binding by WT calreticulin and mutant calreticulin associated with type I myeloproliferative neoplasms, as well as the impact on Ca2+ fluxes in suspension cultures of megakaryocyte-like cells in vitro in response to ER Ca2+ ATPase inhibitors that deplete endoplasmic reticulum (ER) Ca2+ store and open plasma membrane Ca2+ channels through STIM1-Orai interactions. The results are important in that they show that Ca2+ binding by calreticulin and store-operated Ca2+ entry are not fundamentally impacted by the type I deletion mutation in calreticulin, which rules out a direct effect of the calreticulin mutation on its own low-affinity Ca2+ binding and any broad impact on ER Ca2+ regulation. The strength of the data and methods used ranges from solid to convincing, although the use of suspension-based flow cytometric assays to investigate ER Ca2+ levels and Ca2+ entry can be challenged. High-affinity Ca2+ binding sites could be further considered, and possible confounding effects of Abl kinase activity in the megakaryocyte-like cell lines could be offset.

eLife Assessment

This valuable paper advances understanding of the role of the HGF receptor, MET, in cancer cell invasion by demonstrating HGF-induced coordinated trafficking of MET and metalloprotease MT1-MMP into invadopodia. The results are generally solid, but there are concerns about the cell biology and whether the trafficking mechanism is clinically relevant. It's also unclear whether this is a general mechanism or specific to triple-negative breast cancer cells. The paper will be of interest to cancer cell biologists.

eLife Assessment

In this study, the authors investigate the role of ZMAT3, a p53 target gene, in tumor suppression and RNA splicing regulation. Using quantitative proteomics, the authors uncover that ZMAT3 knockout leads to upregulation of HKDC1, a gene linked to mitochondrial respiration, and that ZMAT3 suppresses HKDC1 expression by inhibiting c-JUN-mediated transcription. This set of convincing evidence reveals a fundamental mechanism by which ZMAT3 contributes to p53-driven tumor suppression by regulating mitochondrial respiration.

eLife Assessment

Glioblastoma is among the most aggressive cancers without a cure, and its cells are characterized by high mitochondrial membrane potential. This manuscript provides convincing evidence that glioblastoma tumorigenesis is closely linked to mitochondrial stress. The study makes a valuable contribution to the field by advancing our understanding of the metabolic mechanisms driving glioblastoma and highlighting potential therapeutic targets.

eLife Assessment

This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model points to the case of possible punctuated evolution rather than gradual genomic change. There was some disagreement amongst the reviewers in terms of how closely the theoretical results apply to the phenomena examined empirically, and alternative explanations should be considered in the future.

eLife Assessment

This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.

eLife Assessment

This important study provides solid evidence to support the anti-tumor potential of citalopram, originally an anti-depression drug, in hepatocellular carcinoma (HCC). In addition to their previous report on directly targeting tumor cells via glucose transporter 1 (GLUT1), the authors tried to uncover additional working mechanisms of citalopram in HCC treatment in the current study. The data here suggests that citalopram may regulate the phagocytotic function of TAM via C5aR1 or CD8+T cell function to suppress HCC growth in vivo.

eLife Assessment

This important study describes a deep learning framework that analyzes single-cell RNA data to identify a tumor-agnostic gene signature associated with brain metastases. The identified signature uncovers key molecular mechanisms, highlights potential therapeutic targets, and demonstrates a metastasis-specific transcriptional signal in circulating platelets, suggesting its promise for non-invasive diagnostics through liquid biopsy. The evidence supporting the findings is solid, utilizing interpretable deep learning methodologies and large-scale datasets across multiple cancer types, though some aspects may benefit from additional analysis and validation.

eLife Assessment

This potentially valuable work aimed at a better understanding of the mechanisms of response and resistance to androgen deprivation therapy in prostate cancer using genetically engineered mouse models. A key observation relates to the timing of TNF blockage therapy and the concept of a "TNF switch." The solid data were collected using conventional approaches and the conclusions are mostly justified, particularly with the inclusion of more detailed statistics in the revision. The work will be of interest to the prostate cancer research community.