Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils

Proceedings of the National Academy of Sciences of the United States of America
Nathaniel RobichaudNahum Sonenberg

Abstract

The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation promote metastasis in mouse models of breast cancer by selectively augmenting the translation of mRNAs involved in invasion and metastasis. However, the impact of translational control in cell types within the tumor microenvironment (TME) is unknown. Here, we demonstrate that regulatory events affecting translation in cells of the TME impact cancer progression. Mice bearing a mutation in the phosphorylation site of eIF4E (S209A) in cells comprising the TME are resistant to the formation of lung metastases in a syngeneic mammary tumor model. This is associated with reduced survival of prometastatic neutrophils due to decreased expression of the antiapoptotic proteins BCL2 and MCL1. Furthermore, we demonstrate that pharmacological inhibition of eIF4E phosphorylation prevent...Continue Reading

References

Feb 1, 1977·Canadian Journal of Physiology and Pharmacology·R R MartelS Galet
Jun 16, 1995·The Journal of Biological Chemistry·B JoshiR E Rhoads
Sep 6, 2007·The Journal of Clinical Investigation·Jeremy R GraffEric G Marcusson
Sep 22, 2007·Journal of Leukocyte Biology·Jean M DaleyJorge E Albina
Dec 7, 2007·Genes & Development·Hans-Guido WendelScott W Lowe
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Luc FuricNahum Sonenberg
Nov 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marcin KowanetzNapoleone Ferrara
Sep 13, 2011·Cancer Cell·Zvi GranotRobert Benezra
Mar 24, 2012·Cancer Cell·Douglas Hanahan, Lisa M Coussens
Dec 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Balachandra K GorentlaXiao-Ping Zhong
Feb 13, 2013·Journal of Leukocyte Biology·Carl F FortinPatrick P McDonald
May 10, 2013·PLoS Genetics·Eva BjurCiriaco A Piccirillo
Aug 31, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wenjuan WuRichard A Walgren
Sep 17, 2014·World Journal of Biological Chemistry·Sonali Joshi, Leonidas C Platanias
Oct 4, 2014·Journal of Cell Death·Jenna M McCracken, Lee-Ann H Allen
Mar 7, 2015·Nature Reviews. Drug Discovery·Mamatha BhatIvan Topisirovic
Apr 18, 2015·Breast Cancer Research : BCR·Sébastien TabarièsPeter M Siegel
Jun 20, 2015·Cell·UNKNOWN Cancer Genome Atlas Network
Dec 10, 2015·Mediators of Inflammation·Zvi Granot, Jadwiga Jablonska
May 10, 2016·The Journal of Clinical Investigation·Rebecca LockKaren Cichowski
Jul 2, 2016·Molecular Cancer Research : MCR·Jonathan B BellLeonidas C Platanias
Feb 12, 2017·Cell·Padmanee SharmaAntoni Ribas
Jun 6, 2017·Current Opinion in Cell Biology·Nathaniel Robichaud, Nahum Sonenberg
Jun 15, 2017·Immunology and Cell Biology·María Salvador-BernáldezJesús M Salvador
Aug 24, 2017·The FEBS Journal·Kellie A MouchemoreJohn A Hamilton
Dec 15, 2017·The FEBS Journal·Joanna ObaczEric Chevet

❮ Previous
Next ❯

Citations

Jul 26, 2018·Journal of Leukocyte Biology·Carolyne K Smith, Giorgio Trinchieri
Jun 11, 2020·International Journal of Molecular Sciences·Sathyen A PrabhuSonia V Del Rincón
May 16, 2019·Wiley Interdisciplinary Reviews. RNA·June Bryan I de la PeñaZachary T Campbell
Jun 22, 2019·Annual Review of Biochemistry·Jerry Pelletier, Nahum Sonenberg
May 8, 2020·Acta Neuropathologica Communications·Albert Z HuangPoul H Sorensen
Aug 1, 2020·Cancers·Thao N D PhamHidayatullah G Munshi
Jul 1, 2018·Cold Spring Harbor Perspectives in Biology·Christopher G Proud
Apr 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xuexia LiWen Yi
Oct 18, 2020·Trends in Cancer·Laura J LeeLynne-Marie Postovit
Jan 15, 2021·Journal of Cell Science·Rachael C L SmithOwen J Sansom
Jan 23, 2021·Cancer Research·Douglas S MicalizziShyamala Maheswaran
Oct 27, 2020·Frontiers in Immunology·Mengyue WuXia Liu
Oct 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Margarita BartishCharlotte Rolny
Jun 15, 2020·Cellular Signalling·Xiaotong YangRuifeng Cao
Mar 11, 2021·The Journal of Clinical Investigation·Fan HuangSonia V Del Rincón
Apr 24, 2021·European Journal of Medicinal Chemistry·Xin JinTao Jiang
May 1, 2021·International Journal of Molecular Sciences·Pavel A SakharovSultan C Agalarov
May 12, 2021·Trends in Cancer·Shruthy Suresh, Kathryn A O'Donnell
May 12, 2021·Cellular Signalling·Lilas AlboushiSeyed Mehdi Jafarnejad
Jul 1, 2021·Trends in Molecular Medicine·Giulia LucibelloPatrick Brest
Aug 4, 2021·Nature Reviews. Cancer·Lucilla FabbriStéphan Vagner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.