Evidence map›Paper›PMID 30755444›Full record

ArticleCancer research2019

Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes.

Nazanin Rohani, Liangliang Hao, Maria S Alexis, Brian A Joughin, Konstantin Krismer, Mira N Moufarrej, Anthony R Soltis, Douglas A Lauffenburger, Michael B Yaffe, Christopher B Burge and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 1 pooled it
10.3field-weighted citation impact, top 1% 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

141 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.

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81 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 2 countries.

Nazanin RohaniKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts. fgertler@mit.edu rohani.nazanin@gmail.com.
Liangliang HaoKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts.
Maria S AlexisDepartment of Biological Engineering, MIT, Cambridge, Massachusetts.
Brian A JoughinKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts.ORCID 0000-0003-1022-9450
Konstantin KrismerKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts.ORCID 0000-0001-8994-3416
Mira N MoufarrejDepartment of Biological Engineering, MIT, Cambridge, Massachusetts.ORCID 0000-0001-8953-4057
Anthony R SoltisDepartment of Biological Engineering, MIT, Cambridge, Massachusetts.ORCID 0000-0002-3394-1275
Douglas A LauffenburgerDepartment of Biological Engineering, MIT, Cambridge, Massachusetts.
Michael B YaffeKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts.ORCID 0000-0002-9547-3251
Christopher B BurgeDepartment of Biology, MIT, Cambridge, Massachusetts.ORCID 0000-0001-9047-5648
Sangeeta N BhatiaKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts.
Frank B GertlerKoch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts. fgertler@mit.edu rohani.nazanin@gmail.com.
IIT@MIT · USBroad Institute · USMassachusetts Institute of Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Tumor Cell Networks CenterU54CA112967 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LAUFFENBURGER, DOUGLAS A · 2004 to 2015
$26.2M
Spatial Segregation of Cell Functioning During MotilityR01GM069668 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WELLS, ALAN · 2004 to 2019
$4.7M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Protein Kinase Signaling and Cell Cycle ControlR01ES015339 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2007 to 2017
$4.3M
Protein Kinase Signaling in the Genotoxic Stress ResponseR35ES028374 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2017 to 2024
$3.9M
Dynamics of Gene and Isoform Regulation during EMT and tumor progressionU01CA184897 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B, GERTLER, FRANK B · 2014 to 2018
$3.4M
Howard Hughes Medical Institute 1122028NCI NIH HHS P30 CA014051NCI NIH HHS U01 CA184897NCI NIH HHS U54 CA112967NIEHS NIH HHS R01 ES015339NIEHS NIH HHS R35 ES028374NIGMS NIH HHS R01 GM069668NIGMS NIH HHS T32 GM087237
6 · The paper itself

Abstract

Acidosis is a fundamental feature of the tumor microenvironment, which directly regulates tumor cell invasion by affecting immune cell function, clonal cell evolution, and drug resistance. Despite the important association of tumor microenvironment acidosis with tumor cell invasion, relatively little is known regarding which areas within a tumor are acidic and how acidosis influences gene expression to promote invasion. Here, we injected a labeled pH-responsive peptide to mark acidic regions within tumors. Surprisingly, acidic regions were not restricted to hypoxic areas and overlapped with highly proliferative, invasive regions at the tumor-stroma interface, which were marked by increased expression of matrix metalloproteinases and degradation of the basement membrane. RNA-seq analysis of cells exposed to low pH conditions revealed a general rewiring of the transcriptome that involved RNA splicing and enriched for targets of RNA binding proteins with specificity for AU-rich motifs. Alternative splicing of Mena and CD44, which play important isoform-specific roles in metastasis and drug resistance, respectively, was sensitive to histone acetylation status. Strikingly, this program of alternative splicing was reversed

Indexed as

Alternative SplicingAcidsAnimalsApoptosisBiomarkers, TumorBreast NeoplasmsCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansHyaluronan ReceptorsMiceMice, Inbred BALB CMice, NudeMicrofilament ProteinsNeoplasm InvasivenessAcidsBiomarkers, TumorCD44 protein, humanEnah protein, humanHyaluronan ReceptorsMicrofilament Proteins

Identifiers

PMID30755444
PMCPMC6467770
OpenAlexW2912606030

What OpenQuestion holds

Textmetadata
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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.