Cancer Biology

Citalopram exhibits immune-dependent anti-tumor effects by modulating C5aR1+ TAMs

1. Fangyuan Dong
2. Shan Zhang
3. Kaiyuan Song
4. Luju Jiang
5. Li-Peng Hu
6. Qing Li
7. Xue-Li Zhang
8. Jun Li
9. Mingxuan Feng
10. Zhi-Wei Cai
11. Hong-Fei Yao
12. Rong-Kun Li
13. Hui Li
14. Jie Chen
15. Xiaona Hu
16. Jiaofeng Wang
17. Chongyi Jiang
18. Helen He Zhu
19. Cun Wang
20. Lin-Tai Da
21. Zhi-Gang Zhang
22. Zhijun Bao
23. Xu Wang
24. Shu-Heng Jiang

• Curated by eLife

  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.

Reviewed by eLife

PTEN restrains SHH medulloblastma growth through cell autonomous and nonautonomous mechanisms

1. Zhimin Lao
2. Salsabiel El Nagar
3. Yinwen Liang
4. Daniel N Stephen
5. Alexandra L Joyner

• Curated by eLife

  eLife Assessment

  This valuable study provides insights into the role of Pten mutations in SHH-medulloblastoma, by using mouse models to resolve the effects of heterozygous vs homozygous mutations on proliferation and cell death throughout tumorigenesis. The experiments presented are convincing, with rigorous quantifications and orthogonal experimentation provided throughout, and the models employing sporadic oncogene induction, rather than EGL-wide genetic modifications, represent an advancement in experimental design. However, additional experimentation focused on a greater characterization of macrophage phenotypes (e.g., microglia vs circulating monocytes) would enhance this study. The work will be of interest to medical biologists studying general cancer mechanisms, as the function of Pten may be similar across tumor types.

Reviewed by eLife

Myosin VI orchestrates estrogen-driven gene expression in breast cancer cells

1. Yukti Hari-Gupta
2. Danielle Lambert
3. Isabel W. Shahid-Fuente
4. Natalia Fili
5. Ália dos Santos
6. Alexandria Sprules
7. Hyejeong Rosemary Kim
8. Alexander W. Cook
9. Peter J.I. Ellis
10. Jesse Aaron
11. Teng-Leong Chew
12. Lin Wang
13. Christopher P. Toseland

Reviewed by PREreview

Identifying tissue states by spatial protein patterns related to chemotherapy response in triple-negative breast cancer

1. Luciana M Luque
2. Mohammad Asif Khan
3. Giuseppe Torrisi
4. Tessa D Green
5. David Hardman
6. Claudia Owczarek
7. Tom A Phillips
8. Debora S Marks
9. Maddy Parsons
10. Chris Sander
11. Linus J Schumacher

• Curated by eLife

  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.

Reviewed by eLife

Molecular and Functional Analysis of Calcium Binding by a Cancer-linked Calreticulin Mutant

1. Ishmael Nii Ayibontey Tagoe
2. Amanpreet Kaur
3. Osbourne Quaye
4. Emmanuel Ayitey Tagoe
5. Nicole Koropatkin
6. Leslie S Satin
7. Malini Raghavan

• Curated by eLife

  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.

Reviewed by eLife

RAB14-dependent tubulovesicular recycling directs MET to invadopodia, promoting TNBC cell invasion

1. Amrita Khamari
2. Atreyee Guria
3. Kiran Tak
4. Rajiv Sharma
5. Yannis Kalaidzidis
6. Sunando Datta

• Curated by eLife

  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.

Reviewed by eLife

p53-induced RNA-binding protein ZMAT3 inhibits transcription of a hexokinase to suppress mitochondrial respiration

1. Ravi Kumar
2. Simon Couly
3. Bruna R Muys
4. Xiao Ling Li
5. Ioannis Grammatikakis
6. Ragini Singh
7. Mary Guest
8. Xinyu Wen
9. Wei Tang
10. Stefan Ambs
11. Lisa M Jenkins
12. Erica C Pehrsson
13. Raj Chari
14. Tsung-Ping Su
15. Ashish Lal

• Curated by eLife

  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.

Reviewed by eLife

Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function

1. Bei Zhang
2. Ting Cai
3. Esha Reddy
4. Yuanna Wu
5. Isha Mondal
6. Yinglu Tang
7. Adaeze Scholastical Gbufor
8. Jerry Wang
9. Yawei Shen
10. Qing Liu
11. Raymond Sun
12. Winson S Ho
13. Rongze Olivia Lu
14. Zhihao Wu

• Curated by eLife

  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.

Reviewed by eLife

Punctuated mutagenesis promotes multi-step evolutionary adaptation in human cancers

1. Christopher Graser
2. Wenbo Wu
3. Cole Christini
4. Mia Petljak
5. Franziska Michor

• Curated by eLife

  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.

Reviewed by eLife

Candida albicans drives colorectal cancer progression by inducing hypoxia signaling

1. Wanqiu Wang
2. Mengqi Yang
3. Fanglei Gong
4. Zhenyu Zhang
5. Yanping Ma
6. Haihuang Li
7. Yu Zhao
8. Changzheng Du
9. Ningning Li
10. Guiwei He
11. Kun Sun

• Curated by eLife

  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.

Reviewed by eLife