Evidence map›Paper›PMID 24691442›Full record

ArticleThe Journal of clinical investigation2014

Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer.

Cunxi Li, Haiting Ma, Yang Wang, Zheng Cao, Ramona Graves-Deal, Anne E Powell, Alina Starchenko, Gregory D Ayers, Mary Kay Washington, Vidya Kamath and 4 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

81 citing papers in PubMed, 131 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. World journal of gastrointestinal oncology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Applicability of Spatial Technology in Cancer Research.Cancer research and treatment · 2024
    Review
  12. Article
  13. Article
  14. Multiplex Immunofluorescence: A Powerful Tool in Cancer Immunotherapy.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

21 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

14 authors at 2 institutions in 1 country.

Cunxi Li
Haiting Ma
Yang Wang
Zheng Cao
Ramona Graves-Deal
Anne E Powell
Alina Starchenko
Gregory D Ayers
Mary Kay Washington
Vidya Kamath
Keyur Desai
Michael J Gerdes
Lila Solnica-Krezel
Robert J Coffey
Vanderbilt University Medical Center · USWashington University in St. Louis · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
TRANSFORMING GROWTH FACTORS IN COLONIC NEOPLASIAR01CA046413 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 1988 to 2016
$8.8M
BIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8M
Integrated Biological Systems Training in OncologyT32CA119925 · NCI · VANDERBILT UNIVERSITY · PI Vivian Gama, William Patrick Tansey · 2008 to 2026
$7.6M
GENETIC ANALYSIS OF CONVERGENT EXTENSION IN ZEBRAFISHR01GM055101 · NIGMS · WASHINGTON UNIVERSITY · PI SOLNICAKREZEL, LILIANNA · 1997 to 2014
$4.5M
Validation of a single cell multiplexed in-situ biomarker analysis platform for pR01CA174377 · NCI · GENERAL ELECTRIC GLOBAL RESEARCH CTR · PI COFFEY, ROBERT J., GERDES, MICHAEL · 2012 to 2016
$3.7M
NCI NIH HHS 5T32-CA009582-25NCI NIH HHS CA174377NCI NIH HHS CA46413NCI NIH HHS P30 CA068485NCI NIH HHS P30-CA68485NCI NIH HHS P50 CA095103NCI NIH HHS P50-CA095103NCI NIH HHS R01 CA046413NCI NIH HHS R01 CA174377NCI NIH HHS R01-CA174377NCI NIH HHS T32 CA009582NCI NIH HHS T32 CA119925NCI NIH HHS T32-CA119925NIGMS NIH HHS GM55101NIGMS NIH HHS R01 GM055101
6 · The paper itself

Abstract

The epithelial-to-mesenchymal transition (EMT) transcriptional program is characterized by repression of E-cadherin (CDH1) and induction of N-cadherin (CDH2), and mesenchymal genes like vimentin (VIM). Placenta-specific 8 (PLAC8) has been implicated in colon cancer; however, how PLAC8 contributes to disease is unknown, and endogenous PLAC8 protein has not been studied. We analyzed zebrafish and human tissues and found that endogenous PLAC8 localizes to the apical domain of differentiated intestinal epithelium. Colon cancer cells with elevated PLAC8 levels exhibited EMT features, including increased expression of VIM and zinc finger E-box binding homeobox 1 (ZEB1), aberrant cell motility, and increased invasiveness. In contrast to classical EMT, PLAC8 overexpression reduced cell surface CDH1 and upregulated P-cadherin (CDH3) without affecting CDH2 expression. PLAC8-induced EMT was linked to increased phosphorylated ERK2 (p-ERK2), and ERK2 knockdown restored cell surface CDH1 and suppressed CDH3, VIM, and ZEB1 upregulation. In vitro, PLAC8 directly bound and inactivated the ERK2 phosphatase DUSP6, thereby increasing p-ERK2. In a murine xenograft model, knockdown of endogenous PLAC8 in colon cancer cells resulted in smaller tumors, reduced local invasion, and decreased p-ERK2. Using MultiOmyx, a multiplex immunofluorescence-based methodology, we observed coexpression of cytosolic PLAC8, CDH3, and VIM at the leading edge of a human colorectal tumor, supporting a role for PLAC8 in cancer invasion in vivo.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsAntigens, CDCadherinsCell Line, TumorColonic NeoplasmsDual Specificity Phosphatase 6HEK293 CellsHumansIntestinal MucosaMiceMitogen-Activated Protein Kinase 1Neoplasm InvasivenessNeoplasm ProteinsProteinsVimentinAntigens, CDCadherinsCDH1 protein, humanCDH3 protein, humanDual Specificity Phosphatase 6DUSP6 protein, humanMAPK1 protein, humanMitogen-Activated Protein Kinase 1Neoplasm ProteinsPLAC8 protein, humanProteinsVimentinZebrafish Proteins

Identifiers

PMID24691442
PMCPMC4001536
OpenAlexW2117691023

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.