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DAXX inhibits cancer stemness and epithelial-mesenchymal transition in gastric cancer.
British Journal of Cancer ( IF 6.4 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41416-020-0800-3 Chaofan Wu 1 , Hui Ding 1 , Shuochen Wang 1 , Yangxin Li 2 , Song-Bai Liu 3 , Xiaoxiao Wang 3 , Jiqing Zheng 1 , Ting Xue 1 , Hesham M Amin 4 , Yao-Hua Song 1 , Jin Zhou 5
British Journal of Cancer ( IF 6.4 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41416-020-0800-3 Chaofan Wu 1 , Hui Ding 1 , Shuochen Wang 1 , Yangxin Li 2 , Song-Bai Liu 3 , Xiaoxiao Wang 3 , Jiqing Zheng 1 , Ting Xue 1 , Hesham M Amin 4 , Yao-Hua Song 1 , Jin Zhou 5
Affiliation
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BACKGROUND
DAXX is a transcription repressor that has been implicated in several types of cancers, but its role in the development of gastric cancer remains unknown.
METHODS
We analysed the expression of DAXX in 83 pairs of gastric cancer samples, including neoplastic and adjacent tissues, and correlated the expression levels with clinical stages. We also investigated the molecular mechanisms by which DAXX downregulation promotes cancer growth using both in vitro and in vivo models.
RESULTS
DAXX was downregulated in advanced gastric cancer samples. The expression of DAXX inversely correlates with that of cancer stem cell markers CD44 and Oct4 in gastric cancer lines. DAXX overexpression in gastric cancer cells inhibited migration, invasion and epithelial- mesenchymal transition (EMT). The inhibition of EMT was achieved through the repression of SNAI3, a key inducer of EMT, by recruiting HDAC-1 into the nucleus. Using a xenograft mouse model, we demonstrated that the MKN45 cells formed smaller tumours when DAXX was overexpressed. Wild-type AGS cells were not able to form tumours in nude mice, but in contrast, formed visible tumours when DAXX was silenced in the cells.
CONCLUSION
We for the first time demonstrated that DAXX functions as a tumour suppressor in gastric cancer by inhibiting stem cell growth and EMT.
中文翻译：
DAXX抑制胃癌的癌变和上皮-间质转化。
背景技术DAXX是一种转录阻遏物，已经牵涉到几种类型的癌症中，但是其在胃癌发展中的作用仍然未知。方法我们分析了DAXX在83对胃癌样品中的表达，包括肿瘤和邻近组织，并将其表达水平与临床分期相关联。我们还研究了DAXX下调使用体外和体内模型促进癌症生长的分子机制。结果DAXX在晚期胃癌样本中被下调。在胃癌系中，DAXX的表达与癌干细胞标志物CD44和Oct4的表达呈负相关。胃癌细胞中DAXX的过度表达抑制迁移，侵袭和上皮-间质转化（EMT）。通过将HDAC-1募集到细胞核中来抑制EMAI的关键诱导因子SNAI3，从而实现对EMT的抑制。使用异种移植小鼠模型，我们证明了DAXX过表达时，MKN45细胞形成了较小的肿瘤。野生型AGS细胞不能在裸鼠中形成肿瘤，但是相反，当DAXX在细胞中沉默时，形成了可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。当DAXX在细胞中沉默时，形成可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。当DAXX在细胞中沉默时，形成可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。
更新日期：2020-04-24
中文翻译：
DAXX抑制胃癌的癌变和上皮-间质转化。
背景技术DAXX是一种转录阻遏物，已经牵涉到几种类型的癌症中，但是其在胃癌发展中的作用仍然未知。方法我们分析了DAXX在83对胃癌样品中的表达，包括肿瘤和邻近组织，并将其表达水平与临床分期相关联。我们还研究了DAXX下调使用体外和体内模型促进癌症生长的分子机制。结果DAXX在晚期胃癌样本中被下调。在胃癌系中，DAXX的表达与癌干细胞标志物CD44和Oct4的表达呈负相关。胃癌细胞中DAXX的过度表达抑制迁移，侵袭和上皮-间质转化（EMT）。通过将HDAC-1募集到细胞核中来抑制EMAI的关键诱导因子SNAI3，从而实现对EMT的抑制。使用异种移植小鼠模型，我们证明了DAXX过表达时，MKN45细胞形成了较小的肿瘤。野生型AGS细胞不能在裸鼠中形成肿瘤，但是相反，当DAXX在细胞中沉默时，形成了可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。当DAXX在细胞中沉默时，形成可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。当DAXX在细胞中沉默时，形成可见的肿瘤。结论我们首次证明DAXX通过抑制干细胞生长和EMT而在胃癌中发挥抑癌作用。
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