Reciprocal regulation of Daxx and PIK3CA promotes colorectal cancer cell growth

Yen Sung Huang, Chang Chieh Wu, Che Chang Chang, Shiu Feng Huang, Hong Yi Kuo, Hsiu Ming Shih

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Upregulation of death-domain-associated protein (Daxx) is strongly associated with diverse cancer types. Among these, the clinicopathological significance and molecular mechanisms of Daxx overexpression in colorectal cancer (CRC) remain unknown. Here, we showed that Daxx expression was increased in both clinical CRC samples and CRC cell lines. Daxx knockdown significantly reduced proliferation activity in CRC cells and tumor growth in a xenograft model. Further studies revealed that Daxx expression could be attenuated by either treatment with the PIK3CA inhibitor PIK-75 or PIK3CA depletion in CRC cells. Conversely, expression of PIK3CA constitutively active mutants could increase Daxx expression. These data suggest that PIK3CA positively regulates Daxx expression. Consistently, the expression levels of PIK3CA and Daxx were positively correlated in sporadic CRC samples. Interestingly, Daxx knockdown or overexpression yielded decreased or increased levels of PIK3CA, respectively, in CRC cells. We further demonstrated that Daxx activates the promoter activity and expression of PIK3CA. Altogether, our results identify a mechanistic pathway of Daxx overexpression in CRC and suggest a reciprocal regulation between Daxx and PIK3CA for CRC cell growth.
原文英語
文章編號367
期刊Cellular and Molecular Life Sciences
79
發行號7
DOIs
出版狀態已發佈 - 7月 2022

ASJC Scopus subject areas

  • 分子醫學
  • 分子生物學
  • 藥理
  • 細胞與分子神經科學
  • 細胞生物學

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