肺癌是最常见的肺原发性恶性肿瘤，绝大多数肺癌起源于支气管粘膜上皮，故亦称支气管肺癌。近50多年来，世界各国特别是工业发达国家，肺癌的发病率和病死率均迅速上升，肺癌目前是全世界癌症死因的第一名。
早期研究已证实肺癌起源于支气管粘膜上皮，局限于基底膜内者称为原位癌癌肿，可向支气管腔内或/和临近的肺组织生长，并可通过淋巴血行或经支气管转移扩散。近来研究人员发现基底干细胞能导致肺鳞癌的发生发展，但其具体分子机制尚未完全明了。
最近，一项刊登在The Journal of Pathology的研究揭示：β-连环蛋白（β-catenin）调控气管基底膜细胞的分化，参与了肺鳞癌的发生发展过程。
研究者发现气管基底膜细胞中β-连环蛋白表达的上调与肺鳞癌的严重程度、上皮细胞的增殖以及细胞间黏附的减少有正相关性。科学家通过抑制β-连环蛋白发现：在表达角蛋白-14（Keratin14）的基底膜细胞中，抑制β-连环蛋白会导致正常气道修复减缓，而当β-连环蛋白信号通路被特异性激活时，基底膜细胞的增殖速度、分化以及上皮-间质转化(epithelial-mesenchymal transitions, EMT)都会大大增加。
体外实验中，研究人员对正常人气管基底膜上皮细胞用药物特异性激活β-catenin，结果也发现细胞的增殖、分化和早期上皮-间质转化加快等类似现象。
总之该项研究表明，气管基底膜细胞中β-连环蛋白的表达与基底膜细胞的分化、肺鳞癌的发生发展有着紧密联系，或许可以成为新的治疗肺癌的靶标。(生物谷 Bioon.com)
doi:10.1002/path.3962
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β-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition.
Giangreco A, Lu L, Vickers C, Teixeira VH, Groot KR, Butler CR, Ilieva EV, George PJ, Nicholson AG, Sage EK, Watt FM, Janes SM.
Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that β-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell β-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness. We demonstrate that transgene-mediated β-catenin inhibition within keratin 14-expressing basal cells delayed normal airway repair while basal cell-specific β-catenin activation increased cell proliferation, directed differentiation and promoted elements of early epithelial-mesenchymal transition (EMT), including increased Snail transcription and reduced E-cadherin expression. These observations are recapitulated in normal human bronchial epithelial cells in vitro following both pharmacological β-catenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall, the data show that airway basal cell β-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer.
