Cancer Biology

Extracellular signal-regulated kinase mediates chromatin rewiring and lineage transformation in lung cancer

1. Yusuke Inoue
2. Ana Nikolic
3. Dylan Farnsworth
4. Alvin Liu
5. Marc Ladanyi
6. Romel Somwar
7. Marco Gallo
8. William W. Lockwood

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to cancer biologists studying cell fate transitions, particularly adenocarcinoma-to-small cell transitions that occur in prostate and lung cancer, which is a timely topic. While there is not a single linear mechanism identified that fully explains Kras-induced neuroendocrine cell fate suppression in all contexts, multiple new findings will likely be built upon by the field. Overall, the data are properly controlled and the key claims are supported.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. All reviewers agreed to share their names with the authors.)

Reviewed by eLife

KSR1- and ERK-dependent Translational Regulation of the Epithelial-to-Mesenchymal Transition

1. Chaitra Rao
2. Danielle E. Frodyma
3. Siddesh Southekal
4. Robert A. Svoboda
5. Adrian R. Black
6. Chittibabu Guda
7. Tomohiro Mizutani
8. Hans Clevers
9. Keith R. Johnson
10. Kurt W. Fisher
11. Robert E. Lewis

• Curated by eLife

  Evaluation Summary:

  This paper demonstrates the involvement of Kinase Suppressor of Ras 1, a protein that acts as a scaffold in the mitogen activated protein kinase (MAPK) signaling cascade, in translational control of epithelial-to-mesenchymal transition. The analysis is thorough and includes both loss-of-function and gain-of-function studies. This study advances our understanding of cancer development.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

High dimensional immunotyping of the obese tumor microenvironment reveals model specific adaptation

1. Cara E Wogsland
2. Hilde E Lien
3. Line Pedersen
4. Pahul Hanjra
5. Sturla M Grondal
6. Rolf A Brekken
7. James B Lorens
8. Nils Halberg

Reviewed by Review Commons

RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy

1. Tomasz Radaszkiewicz
2. Michaela Nosková
3. Kristína Gömöryová
4. Olga Vondálová Blanářová
5. Katarzyna Anna Radaszkiewicz
6. Markéta Picková
7. Ráchel Víchová
8. Tomáš Gybeľ
9. Karol Kaiser
10. Lucia Demková
11. Lucia Kučerová
12. Tomáš Bárta
13. David Potěšil
14. Zbyněk Zdráhal
15. Karel Souček
16. Vítězslav Bryja

• Curated by eLife

  Evaluation Summary:

  Radaszkiewicz and collaborators describe RNF43 as a novel negative regulator of WNT5A-induced signaling in human cells. They demonstrate that RNF43 can interact with proteins in this pathway, namely ROR1, ROR2, VANGL1 and VANGL2. Specifically, they find that, through these interactions, RNF43 can suppress invasive properties of melanoma cells, as well as the development of resistance to BRAF V600E inhibitor. The experiments are well done and well explained; however, they were performed only in an in vitro setting and with a very limited number of cell lines.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Loss of MGA mediated Polycomb repression promotes tumor progression and invasiveness

1. Haritha Mathsyaraja
2. Jonathen Catchpole
3. Emily Eastwood
4. Ekaterina Babaeva
5. Michael Geuenich
6. Pei Feng Cheng
7. Brian Freie
8. Jessica Ayers
9. Ming Yu
10. Nan Wu
11. Kumud R Poudel
12. Amanda Koehne
13. William Grady
14. A McGarry Houghton
15. Yuzuru Shiio
16. David P MacPherson
17. Robert N Eisenman

• Curated by eLife

  Summary:

  The reviewers agreed that the paper provides strong in vivo data for a tumor-suppressive role for Mga in lung carcinogenesis. The authors convincingly show that MGA is important in oncogenesis. We note here that MGA is highly understudied (~200 publications) in and of itself despite its involvement with the MYC network for oncogenesis (~41,000 publications at the current time). Given a protein of 3000 amino acids, the number of potential protein partners and PTMs that might modify its tumor suppressor functions are staggering. However, the reviewers also noted that a previous paper has addressed the same topic and the novelty of the data presented here needs to be better explained and additional experiments are needed to strengthen and expand the new aspects.

  Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Intravital deep-tumor single-beam 3-photon, 4-photon, and harmonic microscopy

1. Gert-Jan Bakker
2. Sarah Weischer
3. Júlia Ferrer Ortas
4. Judith Heidelin
5. Volker Andresen
6. Marcus Beutler
7. Emmanuel Beaurepaire
8. Peter Friedl

• Curated by eLife

  Summary: Nonlinear microscopy is in the unique position that high-resolution images of cells and other tissue components can be obtained in live tissue. However, scattering and absorption limit the penetration depth. The impact of nonlinear microscopy in biomedicine and biology would be much improved if higher imaging depths can be achieved. In this manuscript, the authors show they can accomplish imaging in complex specimens using 3- and 4-photon excitation, deeper in the specimen than comparable optics can accomplish with 2-photon excitation laser scanning microscopy. Using a customised commercial system, the authors have incorporated a high-powered laser source with an OPA and dispersion compensation to generate either 1330nm or 1650nm laser lines with high peak pulse energies at low pulse repetition rates. They then compare the relative capabilities of each laser line in terms of number of fluorescence emission channels measured (skin tumour xenografts), fluorescence bleaching analysis and functional toxicity thresholds and fluorescence signal attenuation (excised murine bone).

  This is a very interesting study with some potentially important findings from a technical perspective. However, there is a disconnect at present between the quality of the work and the quality of the presentation. There are many areas of quantitative imaging and intravital imaging that are well known to those in the direct field, and that are a complete mystery to the vast majority of those that are not. It would therefore be highly beneficial to restructure the manuscript in such a way that the findings can reach the many researchers that could benefit from this powerful approach rather than the few who already use it.

Reviewed by eLife

Convergent organization of aberrant MYB complex controls oncogenic gene expression in acute myeloid leukemia

1. Sumiko Takao
2. Lauren Forbes
3. Masahiro Uni
4. Shuyuan Cheng
5. Jose Mario Bello Pineda
6. Yusuke Tarumoto
7. Paolo Cifani
8. Gerard Minuesa
9. Celine Chen
10. Michael G. Kharas
11. Robert K. Bradley
12. Christopher R. Vakoc
13. Richard P. Koche
14. Alex Kentsis

Reviewed by Review Commons

Gene expression has more power for predicting in vitro cancer cell vulnerabilities than genomics

1. Joshua M. Dempster
2. John M. Krill-Burger
3. James M. McFarland
4. Allison Warren
5. Jesse S. Boehm
6. Francisca Vazquez
7. William C. Hahn
8. Todd R. Golub
9. Aviad Tsherniak

• Curated by eLife

  Summary: The authors propose a new approach to the derivation of cancer signatures and compare the relative impact of gene expression data with respect to other variables, particularly SVN and CVNs. The simplicity of the idea and of the technical approach, to the point of singling out a single gene predictive value, is a positive aspect. There are also critical aspects that will require substantial revision including the underlying influence of tissue specific genes. Overall, the paper provides a good basis for the generation of specific hypotheses that can be followed by additional validation studies at the computational and/or experimental level.

Reviewed by eLife

Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a

1. Yuta Nakazawa
2. Nanako Nishiyama
3. Hitoshi Koizumi
4. Kazumasa Kanemaru
5. Chigusa Nakahashi-Oda
6. Akira Shibuya

Reviewed by eLife

The origins and consequences of UPF1 variants in pancreatic adenosquamous carcinoma

1. Jacob T. Polaski
2. Dylan B. Udy
3. Luisa F. Escobar-Hoyos
4. Gokce Askan
5. Steven D. Leach
6. Andrea Ventura
7. Ram Kannan
8. Robert K. Bradley

Reviewed by eLife