CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells.
CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells.
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DOI：
10.1126/sciadv.adi0244
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发表时间：
2023-10-20
期刊：
影响因子：
13.6
通讯作者：
Sanz-Moreno, Victoria
中科院分区：
文献类型：
--
作者：
Samain, Remi;Maiques, Oscar;Monger, Joanne;Lam, Hoyin;Candido, Juliana;George, Samantha;Ferrari, Nicola;Kohihammer, Leonie;Lunetto, Sophia;Varela, Adrian;Orgaz, Jose L.;Vilardell, Felip;Olsina, Jorge Juan;Matias-Guiu, Xavier;Sarker, Debashis;Biddle, Adrian;Balkwill, Frances R.;Eyles, Jim;Wilkinson, Robert W.;Kocher, Hemant M.;Calvo, Fernando;Wells, Claire M.;Sanz-Moreno, Victoria
胰腺导管腺癌（PDAC）由于其高转移倾向及其免疫抑制微环境，预后非常差。使用一组胰腺癌细胞系、三维 (3D) 侵袭系统、微阵列基因特征、微流体装置、小鼠模型和活体成像，我们证明 PDAC 细胞中的 ROCK-肌球蛋白 II 活性支持转录程序，赋予阿米巴样侵袭和免疫抑制特性以及体内转移能力。此外，我们发现免疫检查点 CD73 在变形虫 PDAC 细胞中高表达，并驱动其侵袭、转移和免疫调节特性。从机制上讲，CD73 激活 PI3K 下游的 RhoA–ROCK–肌球蛋白 II。人类 PDAC 活检组织微阵列结合生物信息学分析表明，具有高 CD73-ROCK-Myosin II 活性的圆形变形虫侵袭细胞及其免疫抑制微环境导致患者预后不良。我们建议以变形虫 PDAC 细胞为目标作为治疗策略。 CD73 控制胰腺癌中肌球蛋白 II 驱动的阿米巴入侵和免疫抑制。
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK–Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA–ROCK–Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73–ROCK–Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy. CD73 controls Myosin II driven amoeboid invasion and immunosuppression in pancreatic cancer.
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影响因子：
3.7
作者：
Li NF;Gemenetzidis E;Marshall FJ;Davies D;Yu Y;Frese K;Froeling FE;Woolf AK;Feakins RM;Naito Y;Iacobuzio-Donahue C;Tuveson DA;Hart IR;Kocher HM
通讯作者：
Kocher HM
DOI：
10.1083/jcb.201704053
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Erdogan B;Ao M;White LM;Means AL;Brewer BM;Yang L;Washington MK;Shi C;Franco OE;Weaver AM;Hayward SW;Li D;Webb DJ
通讯作者：
Webb DJ
DOI：
10.1016/j.cub.2015.09.054
发表时间：
2015-11-16
期刊：
Current biology : CB
影响因子：
--
作者：
Cantelli G;Orgaz JL;Rodriguez-Hernandez I;Karagiannis P;Maiques O;Matias-Guiu X;Nestle FO;Marti RM;Karagiannis SN;Sanz-Moreno V
通讯作者：
Sanz-Moreno V
影响因子：
12.3
作者：
Lin W;Noel P;Borazanci EH;Lee J;Amini A;Han IW;Heo JS;Jameson GS;Fraser C;Steinbach M;Woo Y;Fong Y;Cridebring D;Von Hoff DD;Park JO;Han H
通讯作者：
Han H
影响因子：
11.5
作者：
Armstrong, T;Packham, G;Iredale, JP
通讯作者：
Iredale, JP