Evidence map›Paper›PMID 37543570›Full record

ArticleJournal of translational medicine2023

Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis.

Chi-Chiu Lee, Chia-Jui Yu, Sushree Shankar Panda, Kai-Chi Chen, Kang-Hao Liang, Wan-Chen Huang, Yu-Shiuan Wang, Pei-Chin Ho, Han-Chung Wu

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Chi-Chiu LeeInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Chia-Jui YuInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Sushree Shankar PandaInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Kai-Chi ChenInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Kang-Hao LiangInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Wan-Chen HuangInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Yu-Shiuan WangInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Pei-Chin HoBiomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, 11529, Taiwan.
Han-Chung WuInstitute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan. hcw0928@gate.sinica.edu.tw.
Institute of Cellular and Organismic Biology, Academia Sinica · TWAcademia Sinica · TWInstitute of Biomedical Sciences, Academia Sinica · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpithelial cell adhesion molecule (EpCAM) is known to highly expression and promotes cancer progression in many cancer types, including colorectal cancer. While metastasis is one of the main causes of cancer treatment failure, the involvement of EpCAM signaling in metastatic processes is unclear. We propose the potential crosstalk of EpCAM signaling with the HGFR signaling in order to govern metastatic activity in colorectal cancer.

methodsImmunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA), and fluorescence resonance energy transfer (FRET) was conducted to explore the extracellular domain of EpCAM (EpEX) and HGFR interaction. Western blotting was taken to determine the expression of proteins in colorectal cancer (CRC) cell lines. The functions of EpEX in CRC were investigated by proliferation, migration, and invasion analysis. The combined therapy was validated via a tail vein injection method for the metastasis and orthotopic colon cancer models.

resultsThis study demonstrates that the EpEX binds to HGFR and induces downstream signaling in colon cancer cells. Moreover, EpEX and HGF cooperatively mediate HGFR signaling. Furthermore, EpEX enhances the epithelial-to-mesenchymal transition and metastatic potential of colon cancer cells by activating ERK and FAK-AKT signaling pathways, and it further stabilizes active β-catenin and Snail proteins by decreasing GSK3β activity. Finally, we show that the combined treatment of an anti-EpCAM neutralizing antibody (EpAb2-6) and an HGFR inhibitor (crizotinib) significantly inhibits tumor progression and prolongs survival in metastatic and orthotopic animal models of colon cancer.

conclusionOur findings illuminate the molecular mechanisms underlying EpCAM signaling promotion of colon cancer metastasis, further suggesting that the combination of EpAb2-6 and crizotinib may be an effective strategy for treating cancer patients with high EpCAM expression.

Indexed as

Colonic NeoplasmsAnimalsCell Line, TumorCell MovementCrizotinibEpithelial Cell Adhesion MoleculeEpithelial-Mesenchymal TransitionSignal TransductionCrizotinibEpithelial Cell Adhesion MoleculeCancer progressionColorectal cancerEpCAMEpEXEpithelial-to-mesenchymal transitionHGFRInvasion

Identifiers

PMID37543570
PMCPMC10404369
OpenAlexW4385602226

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.