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<p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with rising incidence and mortality rates, in which autophagy plays a pivotal role in promoting tumor survival. Although SEC61G has been reported to be associated with poor outcomes in patients with PDAC, its underlying mechanism remains largely unclear. In the present study, we found that SEC61G was overexpressed in PDAC and correlated with an unfavorable patient prognosis. Further experiments demonstrated the pro-proliferation efficacy of SEC61G in PDAC progression both in vitro and in vivo. Mechanistically, SEC61G enhanced cellular autophagy in PDAC in a Ca<sup>2+</sup> leakage-dependent manner, which could be reversed by thapsigargin treatment. Interestingly, we unveiled that the elevated intracellular Ca²⁺ concentration mediated by SEC61G could activate CREB, phosphorylated CREB bound to the SEC61G promoter and consequently enhanced SEC61G expression. This positive feedback loop may account for the persistent activation of autophagy in PDAC. Our findings highlight the potential of SEC61G as a prognostic biomarker and a therapeutic target candidate for combating PDAC.</p>

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CREB-SEC61G feedback loop sustains enhanced autophagy and boosts proliferation in PDAC

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

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  • Xiao Wu,
  • Xinyan Wu,
  • Yihang Nan,
  • Jianhui Li,
  • Lei Zhuang,
  • Wengang Shan,
  • Song Ge,
  • Kun Tong,
  • Bin Zhang,
  • Qingwei Song,
  • Xuhao Ni

摘要

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with rising incidence and mortality rates, in which autophagy plays a pivotal role in promoting tumor survival. Although SEC61G has been reported to be associated with poor outcomes in patients with PDAC, its underlying mechanism remains largely unclear. In the present study, we found that SEC61G was overexpressed in PDAC and correlated with an unfavorable patient prognosis. Further experiments demonstrated the pro-proliferation efficacy of SEC61G in PDAC progression both in vitro and in vivo. Mechanistically, SEC61G enhanced cellular autophagy in PDAC in a Ca2+ leakage-dependent manner, which could be reversed by thapsigargin treatment. Interestingly, we unveiled that the elevated intracellular Ca²⁺ concentration mediated by SEC61G could activate CREB, phosphorylated CREB bound to the SEC61G promoter and consequently enhanced SEC61G expression. This positive feedback loop may account for the persistent activation of autophagy in PDAC. Our findings highlight the potential of SEC61G as a prognostic biomarker and a therapeutic target candidate for combating PDAC.