Bonastre Ester, Brambilla Elisabeth, Sanchez-Cespedes Montse
Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain.
Department of Pathology, Institut Albert Bonniot, INSERM U823, University Joseph Fourier, CHU, Grenoble Hopital Michallon, Grenoble, France.
J Pathol. 2016 Apr;238(5):606-16. doi: 10.1002/path.4686. Epub 2016 Feb 29.
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.
肺癌是一种致命疾病，大致可分为三个组织病理学类型：肺腺癌、肺鳞状细胞癌（LSCC）和小细胞癌。这些类型的肺癌在分子、表型和区域上都是不同的肿瘤，反映了它们起源细胞的差异。LSCC通常发生在主支气管或叶支气管的气道上皮，这是抵御外部环境的重要防线。此外，大多数LSCC在组织病理学上的特征是存在角化和/或细胞间桥，这与这些肿瘤的分子特征一致，其特征是编码角蛋白以及与细胞间连接和细胞极性相关蛋白质的转录本水平较高。在本综述中，将讨论LSCC的分子特征与起源细胞和上皮类型之间的关系。还将综述LSCC中涉及细胞间粘附和细胞极性的基因的反复改变，强调PAR3和PAR复合物破坏的重要性。最后，将讨论这些改变对上皮稳态可能的功能影响，以及它们如何促进LSCC的发展。
