Cell adhesion and polarity in squamous cell carcinoma of the lung

J Pathol. 2016 Apr;238(5):606-16. doi: 10.1002/path.4686. Epub 2016 Feb 29.

Abstract

Lung cancer is a deadly disease that can roughly be classified into three histopathological groups: lung adenocarcinomas, lung squamous cell carcinomas (LSCCs), and small cell carcinomas. These types of lung cancer are molecularly, phenotypically, and regionally diverse neoplasms, reflecting differences in their cells of origin. LSCCs commonly arise in the airway epithelium of a main or lobar bronchus, which is an important line of defence against the external environment. Furthermore, most LSCCs are characterized histopathologically by the presence of keratinization and/or intercellular bridges, consistent with the molecular features of these tumours, characterized by high levels of transcripts encoding keratins and proteins relevant to intercellular junctions and cell polarity. In this review, the relationships between the molecular features of LSCCs and the types of cell and epithelia of origin are discussed. Recurrent alterations in genes involved in intercellular adhesion and cell polarity in LSCCs are also reviewed, emphasizing the importance of the disruption of PAR3 and the PAR complex. Finally, the possible functional effects of these alterations on epithelial homeostasis, and how they contribute to the development of LSCC, are discussed.

Keywords: DNA sequencing; lung; neoplasia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Adhesion* / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Polarity* / genetics
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Multiprotein Complexes
  • Phenotype

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • PARD3 protein, human