Cancer Biology

High-dimensional immunotyping of tumors grown in obese and non-obese mice

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 repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness

1. Haritha Mathsyaraja
2. Jonathen Catchpole
3. Brian Freie
4. Emily Eastwood
5. Ekaterina Babaeva
6. Michael Geuenich
7. Pei Feng Cheng
8. Jessica Ayers
9. Ming Yu
10. Nan Wu
11. Sitapriya Moorthi
12. Kumud R Poudel
13. Amanda Koehne
14. William Grady
15. A McGarry Houghton
16. Alice H Berger
17. Yuzuru Shiio
18. David MacPherson
19. 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

A statistical framework for assessing pharmacological response and biomarkers using uncertainty estimates

1. Dennis Wang
2. James Hensman
3. Ginte Kutkaite
4. Tzen S. Toh
5. GDSC Screening Team
6. Jonathan R Dry
7. Julio Saez-Rodriguez
8. Mathew J. Garnett
9. Michael P. Menden
10. Frank Dondelinger

Reviewed by eLife

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer

1. Andrea Sacchetti
2. Miriam Teeuwssen
3. Mathijs Verhagen
4. Rosalie Joosten
5. Tong Xu
6. Roberto Stabile
7. Berdine van der Steen
8. Martin M Watson
9. Alem Gusinac
10. Won Kyu Kim
11. Inge Ubink
12. Harmen JG Van de Werken
13. Arianna Fumagalli
14. Madelon Paauwe
15. Jacco Van Rheenen
16. Owen J Sansom
17. Onno Kranenburg
18. Riccardo Fodde

Reviewed by eLife