Cancer Biology

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer

1. Fei Yue
2. Amy T Ku
3. Payton D Stevens
4. Megan N Michalski
5. Weiyu Jiang
6. Jianghua Tu
7. Zhongcheng Shi
8. Yongchao Dou
9. Yi Wang
10. Xin-Hua Feng
11. Galen Hostetter
12. Xiangwei Wu
13. Shixia Huang
14. Noah F Shroyer
15. Bing Zhang
16. Bart O Williams
17. Qingyun Liu
18. Xia Lin
19. Yi Li

• Curated by eLife

  eLife Assessment

  This manuscript presents solid evidence suggesting that the loss of ZNRF3 and RNF43, two E3 ubiquitin ligases, leads to dysregulation of EGFR signaling in cancer. The authors propose that EGFR is a direct substrate of ZNRF3/RNF43. While the authors provide immunoprecipitation data showing increased detection of ubiquitinated species, this evidence does not definitively establish that EGFR itself is ubiquitinated by RNF43/ZNRF3. The absence of direct evidence for EGFR ubiquitination is a major limitation, although the findings are useful as they may provide novel insights into the mechanisms underlying EGFR-driven cancers and open new therapeutic avenues.

Reviewed by eLife

Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women

1. Neil Carleton
2. Sanghoon Lee
3. Ruxuan Li
4. Jian Zou
5. Daniel D Brown
6. Jagmohan Hooda
7. Alexander Chang
8. Rahul Kumar
9. Linda R Klei
10. Lora H Rigatti
11. Joseph Newsome
12. Dixcy Jaba Sheeba John Mary
13. Jennifer M Atkinson
14. Raymond E West
15. Thomas D Nolin
16. Patrick J Oberly
17. Ziyu Huang
18. Donald Poirier
19. Emilia J Diego
20. Peter C Lucas
21. George Tseng
22. Michael T Lotze
23. Priscilla F McAuliffe
24. Ioannis K Zervantonakis
25. Steffi Oesterreich
26. Adrian V Lee

Reviewed by PREreview

Intrinsic bioenergetic adaptations compensate for reduced mitochondrial content in HER2-driven mammary tumors

1. Sara M Frangos
2. Henver S Brunetta
3. Dongdong Wang
4. Maria Joy Therese Jabile
5. David WL Ma
6. William J Muller
7. Cezar M Khursigara
8. Kelsey H Fisher-Wellman
9. Gregory R Steinberg
10. Graham P Holloway

• Curated by eLife

  eLife Assessment

  This useful study uses the MMTV-Neu-YD5 mouse model for HER2-dependent breast cancer to generate transcriptomic and proteomic datasets from extracted primary tumour samples. The data sets generated appear to be solid and will be of interest to the community. However, mechanistic studies to support the conclusion that mitochondrial function is increased in the tumours remain incomplete and would benefit from experiments that would directly interrogate aspects such as cellular heterogeneity, and signalling.

Reviewed by eLife

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in solitary fibrous tumors

1. Connor Hill
2. Alexandra Indeglia
3. Francis Picone
4. Maureen E Murphy
5. Cara Cipriano
6. Robert G Maki
7. Alessandro Gardini

• Curated by eLife

  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.

Reviewed by eLife

Deuterium metabolic imaging phenotypes mouse glioblastoma heterogeneity through glucose turnover kinetics

1. Rui Vasco Simoes
2. Rafael Neto Henriques
3. Jonas L Olesen
4. Beatriz M Cardoso
5. Francisca F Fernandes
6. Mariana AV Monteiro
7. Sune N Jespersen
8. Tânia Carvalho
9. Noam Shemesh

• Curated by eLife

  eLife Assessment

  This study provides a valuable approach to image and analyze in vivo metabolic flux through glucose turnover kinetics in glioblastoma tumor microenvironments. The evidence for the method's validity is convincing, which establishes the dynamic Deuterium Metabolic Imaging technique as an effective tool enabling non-invasive exploration of various tumors.

Reviewed by eLife

Combinatorial CRISPR screen reveals FYN and KDM4 as targets for synergistic drug combination for treating triple negative breast cancer

1. Tackhoon Kim
2. Byung-Sun Park
3. Soobeen Heo
4. Heeju Jeon
5. Jaeyeal Kim
6. Donghwa Kim
7. Sang Kook Lee
8. So-Youn Jung
9. Sun-Young Kong
10. Timothy Lu

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding that synthetically lethal kinase genes FYN and KDM4 may play a role in drug resistance to kinase inhibitors in TNBC. The evidence supporting the claims of the authors is solid, although the exploration of the upstream mechanisms regulating KDM4A or the downstream pathways through which FYN upregulation confers drug resistance would have strengthened the study. The work will be of interest to medical biologists working in the field of breast cancer.

Reviewed by eLife

Plectin-mediated cytoskeletal crosstalk as a target for inhibition of hepatocellular carcinoma growth and metastasis

1. Zuzana Outla
2. Gizem Oyman-Eyrilmez
3. Katerina Korelova
4. Magdalena Prechova
5. Lukas Frick
6. Lenka Sarnova
7. Piyush Bisht
8. Petra Novotna
9. Jan Kosla
10. Patricia Bortel
11. Yasmin Borutzki
12. Andrea Bileck
13. Christopher Gerner
14. Mohammad Rahbari
15. Nuh Rahbari
16. Emrullah Birgin
17. Bibiana Kvasnicova
18. Andrea Galisova
19. Katerina Sulkova
20. Andreas Bauer
21. Njainday Jobe
22. Ondrej Tolde
23. Eva Sticova
24. Daniel Rösel
25. Tracy O'Connor
26. Martin Otahal
27. Daniel Jirak
28. Mathias Heikenwälder
29. Gerhard Wiche
30. Samuel M Meier-Menches
31. Martin Gregor

• Curated by eLife

  eLife Assessment

  This valuable study investigated the role of PLECTIN, a cytoskeletal crosslinker protein, in hepatocellular carcinoma development and progression. Using a liver-specific Plectin knockout mouse model, the authors showed solid evidence that PLECTIN is critical for hepatocarcinogenesis, since inhibition of PLECTIN suppressed tumor formation in multiple models. They also show that PLECTIN is key for HCC invasion and metastasis. They show a correlation between PLECTIN inhibition and attenuated FAK, MAPK/ERK, and PI3K/AKT signaling.

Reviewed by eLife

Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning

1. Gabriella O Estevam
2. Edmond Linossi
3. Jingyou Rao
4. Christian B Macdonald
5. Ashraya Ravikumar
6. Karson M Chrispens
7. John A Capra
8. Willow Coyote-Maestas
9. Harold Pimentel
10. Eric A Collisson
11. Natalia Jura
12. James S Fraser

• Curated by eLife

  eLife Assessment

  This manuscript provides an important overview of potential resistance mutations within MET Receptor Tyrosine Kinase. The evidence supporting the findings is convincing - it should be pointed out that the approach is comparatively new for the application of protein kinases and the results are therefore of potentially great value. The results will be of value for clinicians facing drug resistance mutations, computational biologists who are training models of drug resistance mechanisms and biologists with an interest in cell signaling.

Reviewed by eLife

Non-destructive in situ monitoring of structural changes of 3D tumor spheroids during the formation, migration, and fusion process

1. Ke Ning
2. Yuanyuan Xie
3. Wen Sun
4. Lingke Feng
5. Can Fang
6. Rong Pan
7. Yan Li
8. Ling Yu

• Curated by eLife

  eLife Assessment

  The ingenious design in this study achieved the observation of 3D cell spheroids from an additional lateral view and gained more comprehensive information than the traditional one angle of imaging. This extended the methods to investigate cell behaviors in the growth or migration of tumor organoids in a time-lapse manner and these extensions should be important to the field. The authors provide compelling evidence that the methods work as described.

Reviewed by eLife

Blocking SHP2 benefits FGFR2 inhibitor and overcomes its resistance in FGFR2-amplified gastric cancer

1. Yue Zhang
2. Hanbing Wang
3. Yutao Wei
4. Yunfeng Pan
5. Xueru Song
6. Tao Shi
7. Jie Shao
8. Lixia Yu
9. Baorui Liu
10. Yue Wang
11. Jia Wei

• Curated by eLife

  eLife Assessment

  Based on the perceived low efficacy of current therapies targeted to FGFR2 in gastric cancer (GC), the authors investigate an approach which combines SHP2 inhibition with existing FGFR2 inhibitors. The data were largely collected and analysed using solid and validated methodology. There is some useful data regarding combination therapy in a new clinical cohort, which supports previous studies that have reported the potential of targeting RTKs together with phosphatases.

Reviewed by eLife