Evidence map›Paper›PMID 18558091›Full record

ArticleGastroenterology2008

Constitutive CXCL12 expression induces anoikis in colorectal carcinoma cells.

Michael K Wendt, Luke J Drury, Rebecca A Vongsa, Michael B Dwinell

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 52 citations in OpenAlex.

  1. Clinical Medicine Insights. Oncology · 2026
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  8. The role of vitamin D in hepatic metastases from colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018
    Review
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  16. CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Article
  17. Review
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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

4 authors at 1 institution in 1 country.

Michael K WendtDepartment of Microbiology and Molecular Genetics, Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Luke J Drury
Rebecca A Vongsa
Michael B Dwinell
Medical College of Wisconsin · US

Funding

EPITHELIAL CXCR4 IN A MUCOSAL COMMUNICATION NETWORKR01DK062066 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI DWINELL, MICHAEL B · 2005 to 2009
$1.4M
Epithelial CXCR4 in a Mucosal Communication NetworkR56DK062066 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI DWINELL, MICHAEL B · 2010 to 2010
$329k
NIDDK NIH HHS DK062066NIDDK NIH HHS R01 DK062066NIDDK NIH HHS R56 DK062066
6 · The paper itself

Abstract

BACKGROUND &

aimsCXCL12 and CXCR4 signaling plays critical roles in development, homeostasis, and tumor metastasis. Previously, we have shown that epigenetic silencing of CXCL12 in colorectal and mammary carcinomas promotes metastasis. Anoikis is an essential process of colonic epithelial turnover and limits the metastatic progression of carcinoma. We sought to determine the role for anoikis in limiting tumor metastasis following reexpression of CXCL12 in human colorectal carcinoma cells.

methodsTumor formation and metastasis of colonic carcinoma cells was monitored using in vivo bioluminescence imaging. Anoikis was defined by using caspase-3/7, focal adhesion kinase (FAK) and p130Cas cleavage, DNA fragmentation, and cell survival assays. Phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) was monitored by immunoblot and immunohistochemistry, and activity was inhibited by using U0126.

resultsConstitutive expression of CXCL12 in human colorectal carcinoma cells reduced orthotopic tumor formation and inhibited metastasis in severe combined immunodeficient mice. Further, CXCL12 expression induced apoptosis specifically in nonadherent colorectal carcinoma cells. Apoptotic cell death was preceded by hypophosphorylation and cleavage of FAK and p130Cas, leading to increased cellular detachment in culture, and depended on alterations in the extracellular matrix. Similar to in vivo colonic epithelium, CXCL12-induced anoikis of carcinoma cells depended on basal ERK1/2 activation.

conclusionsThese data significantly expand the current paradigm of chemokine signaling in carcinogenesis by showing that endogenous CXCL12, in marked contrast to exogenous ligand, inhibits tumor metastasis through increased anoikis. Altered ERK1/2 signaling provides a mechanism for the dichotomy between the physiologic and pathophysiologic roles of CXCL12-CXCR4 signaling in the intestinal epithelium.

Indexed as

AnoikisSignal TransductionAnimalsAutocrine CommunicationButadienesCaspase 3Caspase 7Cell AdhesionCell SurvivalChemokine CXCL12Colorectal NeoplasmsCrk-Associated Substrate ProteinDNA FragmentationFocal Adhesion Protein-Tyrosine KinasesFocal AdhesionsHCT116 CellsBCAR1 protein, humanButadienesCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7Chemokine CXCL12Crk-Associated Substrate ProteinCXCL12 protein, humanFocal Adhesion Protein-Tyrosine KinasesMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NitrilesProtein Kinase InhibitorsU 0126

Identifiers

PMID18558091
PMCPMC2583344
OpenAlexW1971867535

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.