Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma

Silvia Vanessa Lourenço1, Cláudia Malheiros Coutinho-Camillo, Marcilei Elisa Cavicchioli Buim

  • 1Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil. silvialourenco.70@terra.com.br

Histopathology
|November 19, 2010
PubMed
Abstract

Insights

Loss of claudin-7 protein expression is common in oral squamous cell carcinoma (OSCC). This down-regulation correlates with tumor size, stage, and poorer survival, suggesting claudin-7 is a key biomarker in OSCC progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Claudins are crucial tight junction proteins frequently dysregulated in human carcinomas.
  • Claudin-7, specifically, shows altered expression patterns in various cancers, necessitating further investigation in oral squamous cell carcinoma (OSCC).

Purpose of the Study:

  • To investigate the expression status and alterations of claudin-7 in oral squamous cell carcinoma (OSCC).
  • To correlate claudin-7 expression with clinical parameters and survival outcomes in OSCC patients.

Main Methods:

  • Claudin-7 protein expression was assessed in 132 OSCC tissue microarrays.
  • Claudin-7 mRNA transcript levels were quantified using real-time polymerase chain reaction.
  • The methylation status of the claudin-7 promoter region was analyzed, with functional studies involving 5-Aza-2'-Deoxycytidine treatment.

Main Results:

  • Claudin-7 protein was found to be negative in 58.3% of OSCC cases.
  • Loss of claudin-7 expression significantly correlated with increased tumor size, advanced clinical stage, recurrence, and reduced disease-free survival.
  • Down-regulation of claudin-7 mRNA was observed in 78% of cases, and promoter methylation was identified as a mechanism for its silencing, reversible with 5-Aza-dC treatment.

Conclusions:

  • Loss of claudin-7 expression is a significant finding in OSCC.
  • Claudin-7 down-regulation is associated with critical subcellular alterations impacting key clinical parameters in OSCC.
  • Claudin-7 may serve as a prognostic biomarker for OSCC.

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Tight Junctions01:29

Tight Junctions

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...