Cancer Biology

Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments

1. Sarah M Chang
2. Muhammad Bin Munim
3. Sonia E Trojan
4. Anna Shevzov-Zebrun
5. Keene L Abbott
6. Matthew G Vander Heiden

• Curated by eLife

  eLife Assessment

  This study presents valuable findings on the relationship between nutrient availability and NAD/NADH levels, which in turn regulate biomass production in cancer cells. The authors provide solid evidence to support their claims, offering insight into why it is difficult to predict which nutrients limit cancer cell growth: both cell type and nutrient availability together determine the oxidative capacity that constrains the synthesis of various metabolic intermediates. The manuscript will be of interest to researchers working in cancer and cell metabolism.

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

Design of combination therapeutics from protein response to drugs in ovarian cancer cells

1. Alexandra Franz
2. Ciyue Shen
3. Fabian Coscia
4. Kenneth Munroe
5. Lea Charaoui
6. Anil Korkut
7. Matthias Mann
8. Augustin Luna
9. Chris Sander

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors provide a simple yet elegant approach to identifying therapeutic targets that synergize to prevent therapeutic resistance in ovarian cancer using cell lines, data-independent acquisition proteomics, and bioinformatic analysis. The authors convincingly identify several combinations of pharmaceuticals that were able to overcome or prevent therapeutic resistance in culture models of ovarian cancer, a disease with an unmet diagnostic and therapeutic need. However, the extent to which these findings may extend to more complex models of ovarian cancer remains unclear.

Reviewed by eLife

Tumoral CD24 tunes platelets binding and pro-metastatic functions

1. Vincent Mittelheisser
2. Cristina Liboni
3. Clarisse Mouriaux
4. Silvia Maria Grazia Trivigno
5. Louis Bochler
6. Maria Garcia-Leon
7. Annabel Larnicol
8. Laetitia Paulen
9. Tristan Stemmelen
10. Pierre Henri Mangin
11. Olivier Lefebvre
12. Jacky G. GOETZ

Reviewed by preLights

PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP

1. Jiongke Wang
2. Yujie Shi
3. Ying Wang
4. Yingqiang Shen
5. Huan Liu
6. Silu Sun
7. Yimei Wang
8. Xikun Zhou
9. Yu Zhou
10. Xin Zeng
11. Jing Li
12. Qianming Chen

• Curated by eLife

  eLife Assessment

  This manuscript determines how PA28g, a proteasome regulator that is overexpressed in tumors, and C1QBP, a mitochondrial protein for maintaining oxidative phosphorylation that plays a role in tumor progression, interact in tumor cells to promote their growth, migration and invasion. Additional experiments and analyses that supported the theoretical models for the interaction have been performed in response to the reviews. The overall findings and conceptual framework are important and the evidence is solid. A logical extrapolation of this work is to test the C1QBP mutants using functional assays to determine whether the mutations can decrease the protein stability mediated by the interaction with PA28g.

Reviewed by eLife

BEHAV3D Tumor Profiler to map heterogeneous cancer cell behavior in the tumor microenvironment

1. Emilio Rios-Jimenez
2. Anoek Zomer
3. Raphael Collot
4. Mario Barrera Román
5. Sandra F Archidona
6. Hendrikus CR Ariese
7. Ravian L van Ineveld
8. Michiel Kleinnijenhuis
9. Nils Bessler
10. Hannah Johnson
11. Caleb A Dawson
12. Anne Rios
13. Maria Alieva

• Curated by eLife

  eLife Assessment

  This is a useful tool for code-less analysis of patterns in cell migratory behaviours in vivo using intravital microscopy data and allows correlation with spatial features of the tumour microenvironment. There is a need for these tools to make quantitative analysis, comparison and interpretation of complex cell tracking data more accessible and evidence is provided of its applicability to tracks generated by both proprietary and open tracking software. However, it is incomplete due to limitations imposed by the assumptions that apply to the statistical tests employed.

Reviewed by eLife

PRMT1-mediated metabolic reprogramming promotes leukemogenesis

1. Hairui Su
2. Yong Sun
3. Han Guo
4. Chiao-Wang Sun
5. Qiuying Chen
6. Szumam Liu
7. Anlun Li
8. Min Gao
9. Rui Zhao
10. Glen Raffel
11. Jian Jin
12. Cheng-Kui Qu
13. Michael Yu
14. Christopher A Klug
15. George Y Zheng
16. Scott Ballinger
17. Matthew Kutny
18. Long X Zheng
19. Zechen Chong
20. Chamara Senevirathne
21. Steven Gross
22. Yabing Chen
23. Minkui Luo
24. Xinyang Zhao

• Curated by eLife

  eLife Assessment

  This study reveals that PRMT1 overexpression drives tumorigenesis of acute megakaryocytic leukemia (AMKL) and that targeting PRMT1 is a viable approach for treating AMKL. After revision, both reviewers found that these findings are important and that the data supporting these findings are convincing. Furthermore, these findings likely have significant implications for the treatment of AMKL with PRMT1 overexpression in the future.

Reviewed by eLife

Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition

1. Laleh S Arabanian
2. Jenni Adamsson
3. Anke Unger
4. Raffaella Di Lucrezia
5. Tim Bergbrede
6. Arghavan Ashouri
7. Erik Larsson
8. Peter Nussbaumer
9. Bert M Klebl
10. Lars Palmqvist
11. Claes M Gustafsson

• Curated by eLife

  eLife Assessment

  This solid study assesses a mitochondrial polymerase inhibitor in combination with the BCL-2 inhibitor venetoclax, with the aim to increase the elimination of acute myeloid leukemia. It provides valuable findings of combinatorial efficacy using preclinical models in vitro and in vivo, confirming the overall importance of targeting oxidative phosphorylation to overcome venetoclax resistance in acute myeloid leukemia, and could be strengthened through mechanistic studies demonstrating on target effects and pharmacodynamic efficacy in vivo. The study is of interest to hematologists because it addresses a key biomedical issue in acute myeloid leukemia (venetoclax resistance) and provides data regarding the safety and activity of a novel inhibitor of the mitochondrial polymerase in combination with venetoclax.

Reviewed by eLife

NOLC1 suppresses immunochemotherapy by inhibiting p53-mediated ferroptosis in gastric cancer

1. Shengsheng Zhao
2. Ji Lin
3. Bingzi Zhu
4. Yin Jin
5. Qiantong Dong
6. Xiaojiao Ruan
7. Dan Jin
8. Yongdong Yi
9. Binglong Bai
10. Hongzheng Li
11. Danna Liang
12. Jianhua Lu
13. Letian Meng
14. Xiang Wang
15. Yuekai Cui
16. Yuyang Gu
17. Xian Shen
18. Xufeng Lu
19. Shangrui Rao
20. Weijian Sun

• Curated by eLife

  eLife Assessment

  This fundamental study identified a novel role of NOLC1 in regulating p53 nuclear transcriptional activity and p53-mediated ferroptosis in gastric cancer. After major revisions, the evidence supporting the conclusions is solid. However, some new experiments are needed to draw more robust conclusions regarding the ferroptosis-associated studies.

Reviewed by eLife

Subtype-specific enhancer RNAs define transcriptional regulators and prognosis in breast cancers

1. Aamena Y Patel
2. Peyman Zarrineh
3. Jigar H Sheth
4. Sumitra Mohan
5. Mudassar Iqbal
6. Sankari Nagarajan

Reviewed by Review Commons