Cancer Biology

HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis

1. Satoshi Takahashi
2. Akinori Kanai
3. Hiroshi Okuda
4. Ryo Miyamoto
5. Yosuke Komata
6. Takeshi Kawamura
7. Hirotaka Matsui
8. Toshiya Inaba
9. Akifumi Takaori-Kondo
10. Akihiko Yokoyama

• Curated by eLife

  Evaluation Summary:

  This manuscript describes the identification and characterization of the interaction between MLL fusion proteins with the HBO1 histone acetyltransferase complex and its role in leukemogenesis. This study adds mechanistic depth into the important recent discovery of HBO1 functions in MLL-fusion leukemias and opens possibilities for a new therapeutic approach.

  (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 #1 agreed to share their name with the authors.)

Reviewed by eLife

The tumor-suppressive long noncoding RNA DRAIC inhibits protein translation and induces autophagy by activating AMPK

1. Shekhar Saha
2. Ying Zhang
3. Briana Wilson
4. Roger Abounader
5. Anindya Dutta

Reviewed by Review Commons

Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms

1. Gary KL Chan
2. Samantha Maisel
3. Yeonjoo C Hwang
4. Bryan C Pascual
5. Rebecca RB Wolber
6. Phuong Vu
7. Krushna C Patra
8. Mehdi Bouhaddou
9. Heidi L Kenerson
10. Huat C Lim
11. Donald Long
12. Raymond S Yeung
13. Praveen Sethupathy
14. Danielle L Swaney
15. Nevan J Krogan
16. Rigney E Turnham
17. Kimberly J Riehle
18. John D Scott
19. Nabeel Bardeesy
20. John D Gordan

• Curated by eLife

  Evaluation Summary:

  In this article, global kinome profiling using fibrolamellar carcinoma and melanoma cell line models was employed to identify key effectors of protein kinase A (PKA) oncogenic signaling, which is hyperactivated in these cancer types. Based on use of molecular and cellular biology assays, authors proposed a model whereby the oncogenic effects of PKA are at least in part mediated by Aurora Kinase A (AURKA)- and PIM2-dependent regulation of MYC family members, and provide evidence that cancers with constitutive activation of PKA may be sensitive to AURKA inhibitors. Overall, it was thought that this study is of broad interest inasmuch as it provides new insights into the molecular underpinnings of oncogenic PKA signaling, and suggests the potential of using AURKA inhibitors to target malignancies characterized by aberrant PKA activation. With stronger mechanistic data linking constitutive PKA signaling to activation of AURKA and PIM2 and MYC regulation and in vivo experiments to support the conclusions, this manuscript will be of interest to researchers in the fields of cancer research, therapeutics, signal transduction and molecular and cell biology.

  (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 #1 agreed to share their name with the authors.)

Reviewed by eLife

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

1. Luca Tirinato
2. Maria Grazia Marafioti
3. Francesca Pagliari
4. Jeannette Jansen
5. Ilenia Aversa
6. Rachel Hanley
7. Clelia Nisticò
8. Daniel Garcia-Calderón
9. Geraldine Genard
10. Joana Filipa Guerreiro
11. Francesco Saverio Costanzo
12. Joao Seco

Reviewed by Review Commons

The novel, recurrent mutation in the TOP2A gene results in the enhanced topoisomerase activity and transcription deregulation in glioblastoma

1. Bartlomiej Gielniewski
2. Katarzyna Poleszak
3. Adria-Jaume Roura
4. Paulina Szadkowska
5. Sylwia K. Krol
6. Rafal Guzik
7. Paulina Wiechecka
8. Marta Maleszewska
9. Beata Kaza
10. Andrzej Marchel
11. Tomasz Czernicki
12. Andrzej Koziarski
13. Grzegorz Zielinski
14. Andrzej Styk
15. Maciej Kawecki
16. Cezary Szczylik
17. Ryszard Czepko
18. Mariusz Banach
19. Wojciech Kaspera
20. Wojciech Szopa
21. Mateusz Bujko
22. Bartosz Czapski
23. Miroslaw Zabek
24. Ewa Izycka-Swieszewska
25. Wojciech Kloc
26. Pawel Nauman
27. Joanna Cieslewicz
28. Bartosz Wojtas
29. Bozena Kaminska

Reviewed by Review Commons

Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference

1. Andrew R Lynch
2. Nicholas L Arp
3. Amber S Zhou
4. Beth A Weaver
5. Mark E Burkard

• Curated by eLife

  Evaluation Summary:

  This study seeks to develop a mathematical framework for estimating rates of chromosome missegregation based on known chromosomal properties and observed aneuploidy rates. A derived model is validated using live-cell imaging before being applied to several previously-described datasets from tumors and organoids. The subject matter is of high interest to aneuploidy and genome evolution researchers.

  (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

BRAFV600E induces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

1. Andrew S McNeal
2. Rachel L Belote
3. Hanlin Zeng
4. Marcus Urquijo
5. Kendra Barker
6. Rodrigo Torres
7. Meghan Curtin
8. A Hunter Shain
9. Robert HI Andtbacka
10. Sheri Holmen
11. David H Lum
12. Timothy H McCalmont
13. Matt W VanBrocklin
14. Douglas Grossman
15. Maria L Wei
16. Ursula E Lang
17. Robert L Judson-Torres

• Curated by eLife

  Evaluation Summary:

  This interesting, timely and well-done study focuses on the mechanism underlying nevus growth arrest, which has received renewed attention as a result of recent studies that question the dogma that such arrest is mediated by oncogene-induced senescence. Through experiments involving both cultured primary human melanocytes and cells derived from clinical samples, the authors show that Braf-oncogene-induced nevus cell growth arrest results from microRNA-dependent suppression of the mitotic kinase Aurkb, which influences whether Braf activity is proliferative versus antiproliferative. While the conclusions made within the manuscript are justified, and there is sound acknowledgment of certain pitfalls that could be addressed in future research, more expansive sample sizes and further in vivo work would aid in providing more clinical relevance. This manuscript would appeal to researchers in the melanoma field, especially those studying the underlying mechanisms behind phenotypic plasticity and tumor heterogeneity.

  (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

Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K

1. John RP Knight
2. Nikola Vlahov
3. David M Gay
4. Rachel A Ridgway
5. William James Faller
6. Christopher Proud
7. Giovanna R Mallucci
8. Tobias von der Haar
9. Christopher Mark Smales
10. Anne E Willis
11. Owen J Sansom

• Curated by eLife

  Evaluation Summary:

  In this study, Knight and colleagues investigate the role of the ribosome and translational control in colorectal tumours. A mutation of a protein of the large ribosomal subunit, RPL24, is used to suppress tumours driven by two mutations found commonly in cancer, in APC and KRAS. The authors identify a mechanistic output of the RPL24 BST mutation, eEF2 phosphorylation, which they demonstrate is a major effector in inhibiting tumour cell translation and proliferation. By targeting the eEF2 kinase eEF2K, they restore protein synthesis in RPL24 mutant cells. The conclusion is well supported by the experimental data presented, which implies that translation elongation can be a potential therapeutic target of KRAS mutated CRC. Importantly, Rpl24Bst in wildtype intestine does not affect epithelial cell proliferation and differentiation, suggesting that translation elongation can be used as tumour-specific target.

  (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 #1 agreed to share their name with the authors.)

Reviewed by eLife

HOXA9 promotes MYC-mediated leukemogenesis by maintaining gene expression for multiple anti-apoptotic pathways

1. Ryo Miyamoto
2. Akinori Kanai
3. Hiroshi Okuda
4. Yosuke Komata
5. Satoshi Takahashi
6. Hirotaka Matsui
7. Toshiya Inaba
8. Akihiko Yokoyama

• Curated by eLife

  Evaluation Summary:

  This manuscript is of potential interest to experimental haematologists studying initiation and maintenance factors in leukaemia. Overall, the study is well designed and the data is clearly presented. However, in some places the analysis lacks depth and technological sophistication, and the novel insights are limited without additional experimentation.

  (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

Effects of the COVID-19 pandemic on publication landscape in chimeric antigen receptor-modified immune cell research

1. Ahmet Yilmaz
2. Jianhua Yu

Reviewed by ScreenIT