Functional antagonism between CagA and DLC1 in gastric cancer

被引：2

作者：

Hinsenkamp, Isabel ^{[1
]}

Koehler, Jan P. ^{[1
]}

Flaechsenhaar, Christoph ^{[1
,2
]}

Hitkova, Ivana ^{[1
]}

Meessen, Sabine Eberhart ^{[1
]}

Gaiser, Timo ^{[2
]}

Wieland, Thomas ^{[3
]}

Weiss, Christel ^{[4
]}

Roecken, Christoph ^{[5
]}

Mowat, Michael ^{[6
]}

Quante, Michael ^{[7
]}

Taxauer, Karin ^{[8
]}

Mejias-Luque, Raquel ^{[8
]}

Gerhard, Markus ^{[8
]}

Vogelmann, Roger ^{[1
]}

Meindl-Beinker, Nadja ^{[1
]}

Ebert, Matthias ^{[1
,9
,10
,11
,12
]}

Burgermeister, Elke ^{[1
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Dept Med 2, Mannheim, Germany

[2] Heidelberg Univ, Med Fac Mannheim, Inst Pathol, Mannheim, Germany

[3] Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Expt Pharmacol, Mannheim, Germany

[4] Heidelberg Univ, Med Fac Mannheim, Dept Med Stat & Biomath, Mannheim, Germany

[5] Christian Albrechts Univ Kiel, Inst Pathol, Kiel, Germany

[6] Univ Manitoba, CancerCare Manitoba Res Inst, Dept Biochem & Med Genet, Winnipeg, MB, Canada

[7] Univ Med Ctr Freiburg, Fac Med, Dept Med Gastroenterol Hepatol Endocrinol & Infec, Freiburg, Germany

[8] Tech Univ Munich TUM, Sch Med, Inst Med Microbiol Immunol & Hyg, Munich, Germany

[9] Univ Med Ctr, DKFZ Hector Inst, Mannheim, Germany

[10] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Innate Immunosci MI3, Mannheim, Germany

[11] Heidelberg Univ, Med Fac Mannheim, Ctr Prevent Med & Digital Hlth, Clin Cooperat Unit Hlth Metab, Mannheim, Germany

[12] Heidelberg Univ, Med Fac Mannheim, Mannheim Canc Ctr MCC, Mannheim, Germany

来源：

CELL DEATH DISCOVERY | 2022年 / 8卷 / 01期

关键词：

TUMOR-GROWTH; RHOA; CELL; CHEMOTHERAPY;

D O I：

10.1038/s41420-022-01134-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Helicobacter (H.) pylori-induced gastritis is a risk factor for gastric cancer (GC). Deleted-in-liver-cancer-1 (DLC1/ARHGAP7) inhibits RHOA, a downstream mediator of virulence factor cytotoxin-A (CagA) signalling and driver of consensus-molecular-subtype-2 diffuse GC. DLC1 located to enterochromaffin-like and MIST1+ stem/chief cells in the stomach. DLC1+ cells were reduced in H. pylori gastritis and GC, and in mice infected with H. pylori. DLC1 positivity inversely correlated with tumour progression in patients. GC cells retained an N-terminal truncation variant DLC1v4 in contrast to full-length DLC1v1 in non-neoplastic tissues. H. pylori and CagA downregulated DLC1v1/4 promoter activities. DLC1v1/4 inhibited cell migration and counteracted CagA-driven stress phenotypes enforcing focal adhesion. CagA and DLC1 interacted via their N- and C-terminal domains, proposing that DLC1 protects against H. pylori by neutralising CagA. H. pylori-induced DLC1 loss is an early molecular event, which makes it a potential marker or target for subtype-aware cancer prevention or therapy.

引用

页数：12

共 33 条

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