Evidence map›Paper›PMID 32348753›Full record

ArticleCell reports2020

Rheb1-Independent Activation of mTORC1 in Mammary Tumors Occurs through Activating Mutations in mTOR.

Bin Xiao, Dongmei Zuo, Alison Hirukawa, Robert D Cardiff, Richard Lamb, Nahum Sonenberg, William J Muller

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Ezh2 promotes mammary tumor initiation through epigenetic regulation of the Wnt and mTORC1 signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Bin XiaoDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind & Morris Goodman Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Dongmei ZuoDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind & Morris Goodman Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Alison HirukawaDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind & Morris Goodman Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Robert D CardiffCenter for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA.
Richard LambUniversity of Liverpool, Liverpool, UK.
Nahum SonenbergDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Faculty of Medicine, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind & Morris Goodman Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada.
William J MullerDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Faculty of Medicine, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind & Morris Goodman Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: william.muller@mcgill.ca.
McGill University Health Centre · CAMcGill University · CAUniversity of California, Davis · USUniversity of Liverpool · GB

Funding

Tyrosine Kinase-Dependant and - Independent Pathways of EGFR in Breast Cancer ProP01CA099031 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MULLER, WILLIAM · 2003 to 2014
$11.6M
Control of Protein Synthesis by the UPS Under StressR01CA202021 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RONAI, ZEEV A. · 2016 to 2020
$2.3M
CIHR FDN-148373NCI NIH HHS P01 CA099031NCI NIH HHS R01 CA202021
6 · The paper itself

Abstract

Mechanistic target of rapamycin complex 1 (mTORC1) is a master modulator of cellular growth, and its aberrant regulation is recurrently documented within breast cancer. While the small GTPase Rheb1 is the canonical activator of mTORC1, Rheb1-independent mechanisms of mTORC1 activation have also been reported but have not been fully understood. Employing multiple transgenic mouse models of breast cancer, we report that ablation of Rheb1 significantly impedes mammary tumorigenesis. In the absence of Rheb1, a block in tumor initiation can be overcome by multiple independent mutations in Mtor to allow Rheb1-independent reactivation of mTORC1. We further demonstrate that the mTOR kinase is indispensable for tumor initiation as the genetic ablation of mTOR abolishes mammary tumorigenesis. Collectively, our findings demonstrate that mTORC1 activation is indispensable for mammary tumor initiation and that tumors acquire alternative mechanisms of mTORC1 activation.

Indexed as

Cell DifferentiationHumansMechanistic Target of Rapamycin Complex 1Mutationras ProteinsSignal TransductionTOR Serine-Threonine KinasesMechanistic Target of Rapamycin Complex 1MTOR protein, humanras ProteinsRHEBL1 protein, humanTOR Serine-Threonine KinasesbreastcancermTORmutationRhebtumorigenesis

Identifiers

PMID32348753
PMCPMC7281837
OpenAlexW3018760458

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.