Cancer is the second leading cause of death worldwide. Key to cancer initiation and progression is the crosstalk between cancer cells and their microenvironment. The extracellular matrix (ECM) is a major component of the tumour microenvironment and integrins, main cell-ECM adhesion receptors, are involved in every step of cancer progression. However, accumulating evidence has shown that integrins can act as tumour promoters but also as tumour suppressor factors, revealing that the biological roles of integrins in cancer are complex. This incites a better understating of integrin function in cancer progression. To achieve this goal, simple model organisms, such asDrosophila, offer great potential to unravel underlying conceptual principles. Here, we find that in theDrosophilawing disc epithelium the βPS integrins act as suppressors of tumours induced by a gain of function of the oncogenic form ofRas,RasV12. We show that βPS integrin depletion enhances the growth, delamination and invasive behaviour ofRasV12tumour cells, as well as their ability to affect the tumour microenvironment. These results strongly suggest that integrin function as tumour suppressors might be evolutionarily conserved.Drosophilacan be used to understand the complex tumour modulating activities conferred by integrins, thus facilitating drug development.
癌症是全球第二大死因。癌症发生与发展的关键在于癌细胞与其微环境之间的相互作用。细胞外基质是肿瘤微环境的主要组成部分，而整合素作为主要的细胞-细胞外基质粘附受体，参与了癌症进展的每一步。然而，越来越多的证据表明，整合素既可以作为肿瘤促进因子，也可以作为肿瘤抑制因子，这揭示了整合素在癌症中的生物学作用具有复杂性。这促使我们更深入地理解整合素在癌症进展中的功能。为实现这一目标，简单的模式生物，如果蝇，为揭示其潜在的概念原理提供了巨大潜力。本研究发现，在果蝇翅盘上皮组织中，βPS整合素可作为由致癌型Ras（RasV12）功能获得所诱导肿瘤的抑制因子。研究表明，βPS整合素的缺失会增强RasV12肿瘤细胞的生长、脱离和侵袭行为，以及它们影响肿瘤微环境的能力。这些结果强烈表明，整合素作为肿瘤抑制因子的功能可能在进化上是保守的。果蝇可用于理解整合素所赋予的复杂肿瘤调节活动，从而促进药物开发。
Integrins Can Act as Suppressors of Ras-Mediated Oncogenesis in theDrosophilaWing Disc Epithelium
肿瘤(癌症)患者之家