Cancer Biology

Replication stress inducing ELF3 upregulation promotes BRCA1-deficient breast tumorigenesis in luminal progenitors

1. Jiadong Zhou
2. Xiao Albert Zhou
3. Li Hu
4. Yujie Ma
5. Jun Zhan
6. Zhanzhan Xu
7. Mei Zhou
8. Qinjian Shen
9. Zhaofei Liu
10. Shaohua Ma
11. Yuntao Xie
12. Jiadong Wang

• Curated by eLife

  eLife Assessment

  In this fundamental study, the authors describe ELF3 as a candidate driver of luminal progenitor transformation, such that its up-regulation during replicative stress conditions and in BRCA1 deficient cells may permit cell proliferation by suppressing genome instability. While the work is certainly of interest, the supporting data remain incomplete as luminal progenitor cells could not be isolated, which would be needed in order to definitively determine whether ELF3 is a driver of transformation in these cells. Overall this paper may offer insight into mechanisms by which BRCA1 deficiency fuels breast tumorigenesis.

Reviewed by eLife

Eliminating Aggressive Cancers via PROTAC-like Inducers of Ferroptosis

1. Avital Oknin-Vaisman
2. Deepanjan Panda
3. Rostislav Novak
4. Eliya Bitman-Lotan
5. Nikolett Pahor
6. Yamen Abu Ahmed
7. Guy Kamnesky
8. Markus E. Diefenbacher
9. Ashraf Brik
10. Amir Orian

Reviewed by Arcadia Science

Formation of malignant, metastatic small cell lung cancers through overproduction of cMYC protein in TP53 and RB1 depleted pulmonary neuroendocrine cells derived from human embryonic stem cells

1. Huanhuan Joyce Chen
2. Eric E Gardner
3. Yajas Shah
4. Kui Zhang
5. Abhimanyu Thakur
6. Chen Zhang
7. Olivier Elemento
8. Harold Varmus

• Curated by eLife

  eLife Assessment

  Given a great need for novel human model systems to study small cell lung cancer (SCLC), the authors describe an important pre-clinical model with broad potential for the study of how genetic perturbations or drug treatments alter SCLC tumor growth, metastasis, and response to therapy. For the major finding, the authors provide convincing evidence that RB/TP53 suppression coupled with MYC overexpression in an ES cell-derived model system results in aggressive and metastatic SCLC. However, the impact of the work would have been increased with the inclusion of a broader set of genetic perturbations, such as over-expression of MYCL, to better model major SCLC phenotypes. The new model described will be of significant interest to researchers studying lung cancer.

Reviewed by eLife

Single-cell profiling reveals the intratumor heterogeneity and immunosuppressive microenvironment in cervical adenocarcinoma

1. Yang Peng
2. Jing Yang
3. Jixing Ao
4. Yilin Li
5. Jia Shen
6. Xiang He
7. Dihong Tang
8. Chaonan Chu
9. Congrong Liu
10. Liang Weng

• Curated by eLife

  eLife Assessment

  In this useful manuscript, the authors performed scRNA-seq on a diverse cohort of 15 early-stage cervical cancer patients. Correlative data is provided to support the possible establishment of an immunosuppressive microenvironment near SCL26A3+ cells, and an association of these cells with upstaging at time of surgery. However without more extensive validation, the evidence supporting the conclusions remains incomplete. Overall, this paper will provide a potentially helpful dataset for researchers studying cervical cancer.

Reviewed by eLife

Monitoring Circulating Cell-free HPV DNA in Metastatic and Recurrent Cervical Cancer: Clinical Importance and Implications for Treatment - A Pilot Study

1. Zhuomin Yin
2. Tao Feng
3. Qing Xu
4. Wumin Dai
5. Maowei Ni
6. Juan Ni
7. Hanmei Lou

• Curated by eLife

  eLife Assessment

  In the field of early detection of disease and recurrence and monitoring of treatment efficacy by cfDNA analysis, this study presents a useful finding that HPV cfDNA level monitoring provides advantages over serum levels of squamous cell carcinoma antigen (SCC-Ag), specifically for HPV+ cervical cancer. The data were collected and analysed using solid and validated methodology but the sample number was limited.

Reviewed by eLife

Rearrangement of 3D genome organization in breast cancer epithelial - mesenchymal transition and metastasis organotropism

1. Priyojit Das
2. Rebeca San Martin
3. Tian Hong
4. Rachel Patton McCord

• Curated by eLife

  eLife Assessment

  This valuable study explores the role of spatial genome organization in oncogenic transformation, addressing an ambitious and significant topic. The authors have assembled comprehensive datasets from various subtypes of localized and lung-metastatic breast cancer cells, as well as from healthy and cancerous lung cells. They identified switching patterns in the 3D genome organization of lung-metastatic breast cancer cells, revealing a reconfiguration of genome architecture that resembles that of lung cells. If validated, this study could be critical for the field; however, at this stage, it is incomplete, as the main claims are only partially substantiated.

Reviewed by eLife

Targeting the Hippo pathway in cancers via ubiquitination dependent TEAD degradation

1. Trang H Pham
2. Kanika Bajaj Pahuja
3. Thijs J Hagenbeek
4. Jason Zbieg
5. Cameron L Noland
6. Victoria C Pham
7. Xiaosai Yao
8. Christopher M Rose
9. Kristen C Browder
10. Ho-June Lee
11. Mamie Yu
12. May Liang-Chu
13. Scott Martin
14. Erik Verschueren
15. Jason Li
16. Marta H Kubala
17. Rina Fong
18. Maria Lorenzo
19. Paul Beroza
20. Peter Hsu
21. Sayantanee Paul
22. Elisia Villemure
23. Wendy Lee
24. Tommy K Cheung
25. Saundra Clausen
26. Jennifer Lacap
27. Yuxin Liang
28. Jason Cheng
29. Steve Schmidt
30. Zora Modrusan
31. Michael Cohen
32. James Crawford
33. Heinrich Jasper
34. Alan Ashworth
35. Jennie R Lill
36. Shiva Malek
37. Joachim Rudolph
38. Ingrid E Wertz
39. Matthew T Chang
40. Xin Ye
41. Anwesha Dey

• Curated by eLife

  eLife Assessment

  This important study describes two findings: first, that TEAD is subject to turnover by the ubiquitin-proteasome system involving RNF146 and Parylation, and second, the development of a pan-TEAD heterobifunctional degrader that is used to inhibit growth of a YAP-dependent cancer cell line and to characterize TEAD binding sites in the genome. Convincing evidence supports the development and specificity of the degrader. This article will be of relevance to cancer biologists and scientists interested in proteostasis, cellular signaling, and post-translation modification of proteins.

Reviewed by eLife

Establishing the foundations for a data-centric AI approach for virtual drug screening through a systematic assessment of the properties of chemical data

1. Allen Chong
2. Ser-Xian Phua
3. Yunzhi Xiao
4. Woon Yee Ng
5. Hoi Yeung Li
6. Wilson Wen Bin Goh

• Curated by eLife

  eLife Assessment

  This study reports valuable findings that highlight the importance of data quality and data representation for ligand-based virtual screening experiments. The authors' claims are supported by solid evidence, although the conclusions have been inferred from only two datasets. The work would gain much impact if additional datasets were used. The main findings will be of interest to cheminformaticians and medicinal chemists working in QSAR modeling, and possibly in other areas related to machine learning.

Reviewed by eLife

The Role of ATP Synthase Subunit e (ATP5I) in Mediating the Metabolic and Antiproliferative Effects of Biguanides

1. Guillaume Lefrançois
2. Emilie Lavallée
3. Marie-Camille Rowell
4. Véronique Bourdeau
5. Farzaneh Mohebali
6. Thierry Berthomeu
7. Mike Tyers
8. Simon-Pierre Gravel
9. Andréea R Schmitzer
10. Gerardo Ferbeyre

• Curated by eLife

  eLife Assessment

  This valuable manuscript describes ATP5I, a subunit of F1Fo-ATP synthase, as a key target of medicinal biguanides, however, it provides incomplete evidence of a direct interaction between ATP5I and metformin. The knockout of ATP5I in pancreatic cancer cells mimics biguanide treatment, inducing a metabolic switch from OXPHOS to glycolysis due to a compromised expression of the Complex I protein NDUFB8. This results in a markedly decreased NAD/NADH ratio and decreased cell proliferation. These findings point out ATP5I as a promising mitochondrial target for cancer therapies and contribute to our understanding of metformin's mechanism of action since many of its molecular mechanisms remain poorly understood.

Reviewed by eLife

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

1. Anne Schreuder
2. Klaas de Lint
3. Mariana M. Góis
4. Rosalie A. Kampen
5. Marta San Martin Alonso
6. Ilse Nootenboom
7. Veronica Garzero
8. Rob M. F. Wolthuis
9. Sylvie M. Noordermeer

Reviewed by Review Commons