Scholarlink

<p>Squamous cell carcinomas (SCCs) originate from various sites that show poor survival due to the presence of cancer stem cells (CSCs), which impart therapy resistance. However, the crosstalk of molecular mechanisms regulating CSCs maintenance in skin and oral SCC is poorly understood. Here, we show that the whole-transcriptome profile of CSCs from skin SCC patients reveals upregulation in expression of genes associated with global hypermethylation, enhanced non-canonical Wnt signaling, and glycolysis, thereby activating the c-Jun/Sox2/Hif1α axis. Thus, it suggests crosstalk among epigenetics/signaling/metabolism in skin and oral SCC. Importantly, the combination of Decitabine (DAC), a methyltransferase inhibitor, and a RAC1 non-canonical Wnt inhibitor (RAC1i) in skin and oral SCC xenograft mouse models reduces global hypermethylation and non-canonical Wnt signaling, thereby attenuating the c-Jun/Sox2/Hif1α axis, stemness, and tumorigenic potential. Overall, our findings show that the combination of DAC and RAC1i may improve the clinical outcomes in patients with skin and oral SCC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Histone methylation defines c-Jun/Sox2/Hif1α axis that controls stemness and tumor progression in squamous cell carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月27日

查看全文
  • Darshan Mehta,
  • Akshay Paradkar,
  • Bharat Rekhi,
  • Prakash Nayak,
  • Bhabani Mohanty,
  • Pradip Chaudhari,
  • Poonam Gera,
  • Swapnil Rane,
  • Pankaj Chaturvedi,
  • Sanjeev K. Waghmare

摘要

Squamous cell carcinomas (SCCs) originate from various sites that show poor survival due to the presence of cancer stem cells (CSCs), which impart therapy resistance. However, the crosstalk of molecular mechanisms regulating CSCs maintenance in skin and oral SCC is poorly understood. Here, we show that the whole-transcriptome profile of CSCs from skin SCC patients reveals upregulation in expression of genes associated with global hypermethylation, enhanced non-canonical Wnt signaling, and glycolysis, thereby activating the c-Jun/Sox2/Hif1α axis. Thus, it suggests crosstalk among epigenetics/signaling/metabolism in skin and oral SCC. Importantly, the combination of Decitabine (DAC), a methyltransferase inhibitor, and a RAC1 non-canonical Wnt inhibitor (RAC1i) in skin and oral SCC xenograft mouse models reduces global hypermethylation and non-canonical Wnt signaling, thereby attenuating the c-Jun/Sox2/Hif1α axis, stemness, and tumorigenic potential. Overall, our findings show that the combination of DAC and RAC1i may improve the clinical outcomes in patients with skin and oral SCC.