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Cited by 62Barrier Structure and Function StudiesCell Adhesion Molecules ResearchCancer Cells and Metastasis

Claudin-3 overexpression increases the malignant potential of colorectal cancer cells: roles of ERK1/2 and PI3K-Akt as modulators of EGFR signaling

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de Souza, Waldemir F., Fortunato-Miranda, Natalia, Robbs, Bruno K., de Araujo, Wallace M., de-Freitas-Junior, Julio C., Bastos, Lilian G., Viola, João P. B., Morgado-Díaz, José A.·2013·PLoS ONE
DOI 10.1371/journal.pone.0074994PMC PMC3777902
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Abstract

The altered expressions of claudin proteins have been reported during the tumorigenesis of colorectal cancer. However, the molecular mechanisms that regulate these events in this cancer type are poorly understood. Here, we report that epidermal growth factor (EGF) increases the expression of claudin-3 in human colorectal adenocarcinoma HT-29 cells. This increase was related to increased cell migration and the formation of anchorage-dependent and anchorage-independent colonies. We further showed that the ERK1/2 and PI3K-Akt pathways were involved in the regulation of these effects because specific pharmacological inhibition blocked these events. Genetic manipulation of claudin-1 and claudin-3 in HT-29 cells showed that the overexpression of claudin-1 resulted in decreased cell migration; however, migration was not altered in cells that overexpressed claudin-3. Furthermore, the overexpression of claudin-3, but not that of claudin-1, increased the tight junction-related paracellular flux of macromolecules. Additionally, an increased formation of anchorage-dependent and anchorage-independent colonies were observed in cells that overexpressed claudin-3, while no such changes were observed when claudin-1 was overexpressed. Finally, claudin-3 silencing alone despite induce increase proliferation, and the formation of anchoragedependent and -independent colonies, it was able to prevent the EGF-induced increased malignant potential. In conclusion, our results show a novel role for claudin-3 overexpression in promoting the malignant potential of colorectal cancer cells, which is potentially regulated by the EGF-activated ERK1/2 and PI3K-Akt pathways.

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  • Claudin-3 has been shown to control malignancy and metastasis in CRC.

    “Whereas claudin-3 has been shown to control malignancy and metastasis in CRC,52,53 claudin-2 led to a leaky epithelium in tumour tissue.54”

    From PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells (2022) · cites this paper as [53]

    The Discussion reports that claudin-3 overexpression increased the malignant potential of HT-29 colorectal cancer cells. The Abstract reports increased colony formation, but says claudin-3 overexpression did not alter migration. Our copy does not show that claudin-3 controls metastasis; the Discussion’s mention of lymph-node metastases concerns claudin-1. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
de Souza, W. F., Fortunato-Miranda, N., Robbs, B. K., de Araujo, W. M., de-Freitas-Junior, J. C., Bastos, L. G., Viola, J. P. B., & Morgado-Díaz, J. A.
Affiliations
Instituto Nacional de Câncer - INCA (BR)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-09-19
Volume
8
Issue
9
Pages
e74994
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0074994
PMC
PMC3777902
OpenAlex
W1971911299
Cited by
62
References
1
Citations by year
2026: 1 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 2
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (573806/2008-0, 170.026/2008)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (-0 and, #573806/2008-0, 170.026/2008)
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (170.026/2008, 573806/2008-0)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
claudin-3, claudin-1, colorectal cancer, EGFR signaling, epidermal growth factor, MAPK/ERK pathway, PI3K/Akt signaling, cell migration, anchorage-independent colony formation, tight junctions, tumor malignancy, HT-29 cells
MeSH terms
Cell Movement, Cell Transformation, Neoplastic, Epidermal Growth Factor, Humans, Tumor Stem Cell Assay, Colorectal Neoplasms, Signal Transduction, Gene Expression, Gene Expression Regulation, Neoplastic, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Gene Silencing, Protein Transport, Cell Line, Tumor, Mitogen-Activated Protein Kinase 3, Cell Proliferation, Proto-Oncogene Proteins c-akt, Claudin-1, Claudin-3, ErbB Receptors

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