Department of Developmental Biology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
PLoS One. 2022 Jan 14;17(1):e0262360. doi: 10.1371/journal.pone.0262360. eCollection 2022.
Over the years Ski and Sno have been found to be involved in cancer progression e.g. in oesophageal squamous cell carcinoma, melanoma, oestrogen receptor-positive breast carcinoma, colorectal carcinoma, and leukaemia. Often, their prooncogenic features have been linked to their ability of inhibiting the anti-proliferative action of TGF-ß signalling. Recently, not only pro-oncogenic but also anti-oncogenic functions of Ski/Sno proteins have been revealed. Besides Ski and Sno, which are ubiquitously expressed other members of Ski/Sno proteins exist which show highly specific neuronal expression, the SKI Family Transcriptional Corepressors (Skor). Among others Skor1 and Skor2 are involved in the development of Purkinje neurons and a mutation of Skor1 has been found to be associated with restless legs syndrome. But neither Skor1 nor Skor2 have been reported to be involved in cancer progression. Using overexpression studies in the Drosophila eye imaginal disc, we analysed if the Drosophila Skor homologue Fuss has retained the potential to inhibit differentiation and induce increased proliferation. Fuss expressed in cells posterior to the morphogenetic furrow, impairs photoreceptor axon pathfinding and inhibits differentiation of accessory cells. However, if its expression is induced prior to eye differentiation, Fuss might inhibit the differentiating function of Dpp signalling and might maintain proliferative action of Wg signalling, which is reminiscent of the Ski/Sno protein function in cancer.
多年来，Ski 和 Sno 已被发现参与癌症的进展，例如在食管鳞状细胞癌、黑色素瘤、雌激素受体阳性乳腺癌、结直肠癌和白血病中。通常，它们的致癌特征与其抑制 TGF-β信号的抗增殖作用的能力有关。最近，Ski/Sno 蛋白不仅具有致癌作用，而且具有抗癌作用。除了广泛表达的 Ski 和 Sno 之外，Ski/Sno 蛋白的其他成员还存在高度特异性的神经元表达，即 Ski/Sno 家族转录共抑制因子（Skor）。其中，Skor1 和 Skor2 参与浦肯野神经元的发育，并且已经发现 Skor1 的突变与不安腿综合征有关。但是，Skor1 或 Skor2 均未被报道参与癌症进展。通过在果蝇眼睛 imaginal 盘的过表达研究，我们分析了果蝇 Skor 同源物 Fuss 是否保留了抑制分化和诱导增殖的潜力。在形态发生沟后表达的 Fuss 会损害光感受器轴突的寻路，并抑制辅助细胞的分化。然而，如果在眼睛分化之前诱导其表达，Fuss 可能会抑制 Dpp 信号的分化功能，并可能维持 Wg 信号的增殖作用，这让人联想到 Ski/Sno 蛋白在癌症中的功能。
