School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
Leicester Institute for Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK.
Open Biol. 2021 Sep;11(9):210077. doi: 10.1098/rsob.210077. Epub 2021 Sep 8.
Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in , reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.
大约 90%的癌症相关死亡可归因于肿瘤的扩散能力。我们已经确定 CG7379 是苍蝇与人 ING1 的同源物,是一种有效的侵袭抑制因子。ING1 是一种 II 型肿瘤抑制因子,在控制细胞增殖、对 DNA 损伤的反应、致癌基因诱导的衰老和细胞凋亡的基因的转录调控中具有明确的作用。最近的工作表明 ING1 可能在癌细胞侵袭和转移中发挥作用,但缺乏对这一观察结果的分子机制的了解。我们的结果表明,CG7379 的表达减少促进了侵袭,减少了几个黏附连接和隔膜连接成分的连接定位,并严重破坏了细胞-细胞连接结构。类似地,ING1 的敲低显著增强了侵袭,并破坏了细胞-细胞连接处 E-钙粘蛋白的分布。转录组分析表明,ING1 的缺失会影响几个连接和细胞骨架调节剂的表达,证实了 ING1 作为侵袭抑制因子和细胞-细胞连接完整性的关键调节剂的作用。