Cell reports · 2026
SPINK1-COL18A1 crosstalk shapes epigenome and drives cancer stemness in pancreatic ductal adenocarcinoma.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Tang Haoyu, Sailo Bethsebie, Shang Xingbo, Hossan Md Shahadat, Kratz Jeremy, Das Paromita, Chhoda Ankit, Aldo Paulomi, Liu He, Robert Marie E, Doucette Saryn, Paris Timothy J, Kunstman John W, Pappou Emmanouil, Wood Laura D, Iacobuzio-Donahue Christine A, Wolfgang Christopher L, Mazzetto Mariateresa, He Linda, Pfaff Marie, Ang-Olson Olivia, Hoggard Timothy, Garcia-Milian Rolando, Sharma Anup, Levchenko Andre, Ahuja Nita
Аннотация
Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with increasing incidence and a dismal prognosis. Here, we uncover serine protease inhibitor Kazal type 1 (SPINK1) as a putative determinant of PDAC progression with a previously unrecognized role in epigenomic regulation. We show that SPINK1 expression, which is highly dynamic across PDAC progression, is associated with key aggressive cancer phenotypic states and regulates cancer cell stemness and plasticity in both in vitro and patient samples. Mechanistically, our results suggest a new signaling axis where SPINK1 interacts with COL18A1 to promote its cleavage into endostatin, which then induces histone H3 modifications. These results reveal a new function of SPINK1 in PDAC and highlight the SPINK1-COL18A1-endostatin signaling axis as a potential therapeutic target to combat PDAC aggressiveness.