5月31日，瑞典卡羅林斯卡醫(yī)學院宣布發(fā)現(xiàn)了胰腺癌細胞變化的新機理，這將有助于胰腺癌的早期診斷。

根據(jù)現(xiàn)有研究成果，胰腺癌與以下兩種特殊的細胞結構變化有關：RAS致癌基因發(fā)生突變；大量分子信號是按照一種“刺猬”式信號傳遞的。

瑞典卡羅林斯卡醫(yī)學院的研究人員在對老鼠實驗后，發(fā)現(xiàn)了RAS基因和“刺猬”式信號傳遞相互作用的機理。當RAS基因被激活時，腫瘤細胞就會分泌SHH，這種物質會引發(fā)“刺猬”式信號傳遞活動，同時阻止腫瘤細胞對這種信號做出反應。整個過程分為兩個階段：*階段在“刺猬”式信號刺激下，腫瘤細胞周圍的細胞會迅速生長，而腫瘤細胞在SHH保護下處于安全狀態(tài)；第二階段當SHH的作用消失時，腫瘤細胞在“刺猬”式信號的刺激下加速生長，腫瘤開始逐漸惡化，直至形成癌癥。

這一成果發(fā)表在新一期《自然·結構與分子生物學》雜志上。

上海勁馬生物（）推薦原文出處：

Nature Structural & Molecular Biology  doi:10.1038/nsmb.1833

DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS
Matthias Lauth1,4, ?sa Bergstr?m1, Takashi Shimokawa1, Ulrica Tostar1, Qianren Jin1, Volker Fendrich2, Carmen Guerra3, Mariano Barbacid3 & Rune Toftg?rd1

Synergism between the RAS and Hedgehog （HH） pathways has been suggested for carcinogenesis in the pancreas, lung and colon. We investigated the molecular cross-talk between RAS and HH signaling and found that, although mutant RAS induces or enhances SHH expression and favors paracrine HH signaling, it antagonizes autocrine HH signal transduction. Activated RAS can be found in primary cilia, the central organelle of HH signal transduction, but functions in a cilium-independent manner and interferes with Gli2 function and Gli3 processing. In addition, the cell-autonomous negative regulation of HH signal transduction involves the RAS effector molecule dual specificity tyrosine phosphorylated and regulated kinase 1B （DYRK1B）. In line with a redirection of autocrine toward paracrine HH signaling by a KRAS-DYRK1B network, we find high levels of GLI1 expression restricted to the stromal compartment and not to SHH-expressing tumor cells in human pancreatic adenocarcinoma.