Evidence map›Paper›PMID 30932013›Full record

ArticleCell death and differentiation2019

The KRAS-variant and its impact on normal breast epithelial cell biology.

Song-Yi Jung, Poonam Malhotra, Kiana C Nguyen, David Salzman, Yue Qi, Ethan H Pak, Joshua King, Erina Vlashi, David Ann, Joanne B Weidhaas

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. 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

10 authors at 2 institutions in 1 country.

Song-Yi JungDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Poonam MalhotraDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Kiana C NguyenDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
David SalzmanDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Yue QiDepartment of Diabetes Complications and Metabolism, City of Hope, Duarte, CA, 91010, USA.
Ethan H PakDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Joshua KingDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
Erina VlashiDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA.
David AnnDepartment of Diabetes Complications and Metabolism, City of Hope, Duarte, CA, 91010, USA.
Joanne B WeidhaasDepartment of Radiation Oncology, University of California, Los Angeles, CA, USA. jweidhaas@mednet.ucla.edu.
University of California, Los Angeles · USCity of Hope · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
Epigenetic damage in women living in LA food-desert zip codesR01CA220693 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ANN, DAVID K., HYSLOP, TERRY · 2017 to 2021
$3.7M
MicroRNAs to Understand Cause and Outcome in Breast CancerR01CA157749 · NCI · YALE UNIVERSITY · PI SLACK, FRANK J., WEIDHAAS, JOANNE B · 2012 to 2016
$1.7M
NCI NIH HHS P30 CA033572NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA157749NCI NIH HHS R01 CA220693U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA157749
6 · The paper itself

Abstract

MicroRNA (miRNA)-binding site variants in 3' untranslated regions (3'UTRs) are a novel class of germ-line, functional mutations, which are now recognized as powerful biomarkers of human cancer risk and biology. The first mutation discovered in this class is the KRAS-variant, a let-7-binding site mutation in the 3'UTR of the KRAS oncogene. The KRAS-variant predicts increased cancer risk for certain populations, is a predictive biomarker of cancer treatment response across cancer types, leads to conserved tumor biology and elevated AKT signaling in KRAS-variant patient tumors, and was recently found to predict elevated TGF-β and immunosuppression in cancer patients. Based on the functional biology of the KRAS-variant in cancer patients, here we chose to investigate altered normal cellular biology in the presence of the KRAS-variant, through interrogation of an isogenic normal breast epithelial cell line model with and without the KRAS-variant. We find that KRAS-variant normal breast epithelial cells exhibit a mesenchymal phenotype, which appears to be due to numerous molecular changes, including miRNA dysregulation and autocrine pathway alterations, including elevated TGF-β, resulting in ZEB and SNAIL upregulation. Our findings support the hypothesis that the KRAS-variant has a fundamental biological impact on normal cellular biology, that is conserved in these patients when they develop cancer.

Indexed as

BreastCell LineEpithelial CellsEpithelial-Mesenchymal TransitionFemaleHumansProto-Oncogene Proteins p21(ras)KRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID30932013
PMCPMC7224195
OpenAlexW2928569849

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.