Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

mTOR dependent transformed human cells have a distinct set of essential genes from bcr-abl transformed cells

Don Benjamin, Marco Colombi, Christoph Moroni, Michael N. Hall
doi: https://doi.org/10.1101/737817
Don Benjamin
Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marco Colombi
Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christoph Moroni
Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael N. Hall
Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: m.hall@unibas.ch
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Constitutively active intracellular signaling drives and sustains cancer growth. The mTOR kinase integrates multiple inputs sensing nutrient, energy and growth factor levels to promote protein synthesis and anabolic metabolism, and is hyperactivated in a broad range of cancers. The bcr-abl kinase is a fusion protein generated by chromosomal translocation and gives rise to chronic myeloid leukemia and a small sub-set of leukemias. Using an in vitro transformed murine cell model, we performed shRNA knockdown of 25 genes previously shown to be essential for mTOR dependent oncogenic growth and survival. None of the genes were essential in the bcr-abl transformed line. Interrogation of this gene set in human cancer cell lines revealed that many of these genes were essential in cells dependent on mTOR signaling (defined by sensitivity to pharmacological mTOR inhibition). However, none of the genes were essential in bcr-abl transformed K562 cells that are insensitive to mTOR inhibition. Thus there is a clear divide between cells transformed via bcr-abl directed oncogenesis and other modes of transformation where mTOR, due to its central role in regulating cell growth and metabolism, is recruited as part of an oncogenic program. These validated hits represent a set of genes essential for executing critical functions downstream of mTOR and may be novel therapeutic targets for cancer.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted August 16, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
mTOR dependent transformed human cells have a distinct set of essential genes from bcr-abl transformed cells
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
mTOR dependent transformed human cells have a distinct set of essential genes from bcr-abl transformed cells
Don Benjamin, Marco Colombi, Christoph Moroni, Michael N. Hall
bioRxiv 737817; doi: https://doi.org/10.1101/737817
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
mTOR dependent transformed human cells have a distinct set of essential genes from bcr-abl transformed cells
Don Benjamin, Marco Colombi, Christoph Moroni, Michael N. Hall
bioRxiv 737817; doi: https://doi.org/10.1101/737817

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4086)
  • Biochemistry (8761)
  • Bioengineering (6479)
  • Bioinformatics (23339)
  • Biophysics (11749)
  • Cancer Biology (9148)
  • Cell Biology (13246)
  • Clinical Trials (138)
  • Developmental Biology (7416)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10398)
  • Genomics (14009)
  • Immunology (9120)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47359)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)