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<p>Metabolic reprogramming, characterized by dysregulated lipid metabolism and consequent endoplasmic reticulum (ER) stress, constitutes a hallmark of pancreatic ductal adenocarcinoma (PDAC). Within this metabolic landscape, the 2′-5′-Oligoadenylate Synthetase (OAS) family member OAS1 is identified as a critical driver of malignancy, exhibiting specific upregulation in PDAC tissues that correlates with poor patient prognosis. Functionally, OAS1 drives tumor progression, including cell proliferation and metastasis, by operating as a non-canonical metabolic regulator. Mechanistically, OAS1 binds to fatty acid synthase (FASN), maintaining its functional protein levels and thereby promoting FASN-dependent lipid synthesis. The resulting surge in de novo lipid synthesis and lipid droplet accumulation precipitates an adaptive ER stress response via the PERK-ATF4 signaling axis. Consequently, a functional OAS1-FASN axis operates to coordinate lipid overload with pro-survival ER stress signaling, establishing OAS1 as a pivotal metabolic regulator and a viable biomarker in PDAC.</p><p></p>

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The OAS1-FASN axis promotes pancreatic cancer by coordinating lipogenic stress and the unfolded protein response

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月3日

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  • Yuheng Zhu,
  • Hongfei Yao,
  • Chunjing Li,
  • Jie Peng,
  • Jieqiong Ge,
  • Meng Liu,
  • Tongyi Zhang,
  • Zhiwei Cai,
  • Chongyi Jiang

摘要

Metabolic reprogramming, characterized by dysregulated lipid metabolism and consequent endoplasmic reticulum (ER) stress, constitutes a hallmark of pancreatic ductal adenocarcinoma (PDAC). Within this metabolic landscape, the 2′-5′-Oligoadenylate Synthetase (OAS) family member OAS1 is identified as a critical driver of malignancy, exhibiting specific upregulation in PDAC tissues that correlates with poor patient prognosis. Functionally, OAS1 drives tumor progression, including cell proliferation and metastasis, by operating as a non-canonical metabolic regulator. Mechanistically, OAS1 binds to fatty acid synthase (FASN), maintaining its functional protein levels and thereby promoting FASN-dependent lipid synthesis. The resulting surge in de novo lipid synthesis and lipid droplet accumulation precipitates an adaptive ER stress response via the PERK-ATF4 signaling axis. Consequently, a functional OAS1-FASN axis operates to coordinate lipid overload with pro-survival ER stress signaling, establishing OAS1 as a pivotal metabolic regulator and a viable biomarker in PDAC.