scholarly journals ADP ribosylation factor guanylate kinase 1 promotes the malignant phenotype of gastric cancer by regulating focal adhesion kinase activation

Life Sciences ◽  
2021 ◽  
pp. 119264
Author(s):  
Sunyun Zhang ◽  
Qiong Luo ◽  
Rui Feng ◽  
Fan Yang ◽  
Qian Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Malignant Phenotype ◽  
Guanylate Kinase ◽  
Kinase Activation ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor

scholarly journals Role of ADP Ribosylation Factor Guanylate Kinase 1 in the Malignant Biological Behavior of Gastric Cancer

2021 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Fan Yang ◽  
Rui Feng ◽  
Qian Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Nude Mice ◽  
Caspase 3 ◽  
Cell Counting ◽  
Biological Behavior ◽  
Guanylate Kinase ◽  
Invasion And Migration ◽  
Adp Ribosylation ◽  
And Migration ◽  
Adp Ribosylation Factor

Abstract Objectives: To study the effects of ADP ribosylation factor guanylate kinase 1 gene (ASAP1) on the biological behavior of malignant gastric cancer (GC), and explore its possible molecular mechanisms in tumorigenesis and tumor progression.Methods: Quantitative PCR and western blotting (WB) were performed to measure ASAP1 mRNA and protein expression in the GES-1 epithelial cell line, which is derived from normal human mucosa, and three GC cell lines. Molecular biology techniques such as lentivirus packaging, infection, and screening were used to obtain BGC823 GC cells overexpressing ASAP1 and BGC823 and MKN45 cells with ASAP1 knocked down. The Cell Counting Kit-8 assay, colony formation assay, flow cytometry using Annexin V/propidium iodide, Transwell migration and invasion assays, and scratch assay were used to assess the malignant biological behavior of GC cells with ASAP1 overexpression and knockdown. WB was conducted to evaluate the effects of ASAP1 expression on angiogenesis, as well as on the expression of matrix metalloproteinases (MMPs), apoptotic proteins, and epithelial-mesenchymal transition (EMT)-related proteins. Nude mice bearing transplanted tumors were evaluated to determine the effect of ASAP1 knockdown on BGC823 GC cells.Results: ASAP1 expression in GC cells was greater than that in GES-1 normal gastric mucosal epithelial cells. ASAP1 overexpression significantly enhanced the proliferation, invasion, and migration of GC cells and reduced apoptosis; whereas ASAP1 knockdown significantly reduced the proliferation, invasion, and migration of GC cells and promoted apoptosis. In the ASAP1-knockdown group, expression of cleaved-caspase 3, cleaved-poly-ADP-ribose polymerase (PARP), and the epithelial marker E-cadherin increased significantly, whereas the expression of MMP2, MMP9, vascular endothelial growth factor A (VEGFA), and the mesenchymal markers N-cadherin, and vimentin decreased significantly (P<0.01). Knockdown of ASAP1 inhibited the growth of subcutaneously implanted tumors in nude mice.Conclusions: ASAP1 overexpression strongly promotes—whereas knockdown of ASAP1 effectively weakens—the malignant biological behavior of GC cells, possibly by reducing VEGFA expression and thus reducing angiogenesis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP, and reducing the activity of MMPs and EMT.

scholarly journals Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer

2019 ◽  
Vol 10 (2) ◽  
pp. 288-305 ◽  
Author(s):  
Haisheng Zhang ◽  
Antje Schaefer ◽  
Yichen Wang ◽  
Richard G. Hodge ◽  
Devon R. Blake ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Diffuse Gastric Cancer ◽  
Gain Of Function ◽  
Kinase Activation

scholarly journals The Association of ASAP1, an ADP Ribosylation Factor-GTPase Activating Protein, with Focal Adhesion Kinase Contributes to the Process of Focal Adhesion Assembly

2002 ◽  
Vol 13 (6) ◽  
pp. 2147-2156 ◽  
Author(s):  
Yunhao Liu ◽  
Joost C. Loijens ◽  
Karen H. Martin ◽  
Andrei V. Karginov ◽  
J. Thomas Parsons
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Ph Domain ◽  
Wild Type ◽  
Gtpase Activating Protein ◽  
Adp Ribosylation ◽  
Transient Overexpression ◽  
Adp Ribosylation Factor

ASAP1 (ADP ribosylation factor [ARF]- GTPase-activating protein [GAP] containing SH3, ANK repeats, and PH domain) is a phospholipid-dependent ARF-GAP that binds to and is phosphorylated by pp60Src. Using affinity chromatography and yeast two-hybrid interaction screens, we identified ASAP1 as a major binding partner of protein tyrosine kinase focal adhesion kinase (FAK). GlutathioneS-transferase pull-down and coimmunoprecipitation assays showed the binding of ASAP1 to FAK is mediated by an interaction between the C-terminal SH3 domain of ASAP1 with the second proline-rich motif in the C-terminal region of FAK. Transient overexpression of wild-type ASAP1 significantly retarded the spreading of REF52 cells plated on fibronectin. In contrast, overexpression of a truncated variant of ASAP1 that failed to bind FAK or a catalytically inactive variant of ASAP1 lacking GAP activity resulted in a less pronounced inhibition of cell spreading. Transient overexpression of wild-type ASAP1 prevented the efficient organization of paxillin and FAK in focal adhesions during cell spreading, while failing to significantly alter vinculin localization and organization. We conclude from these studies that modulation of ARF activity by ASAP1 is important for the regulation of focal adhesion assembly and/or organization by influencing the mechanisms responsible for the recruitment and organization of selected focal adhesion proteins such as paxillin and FAK.

scholarly journals Apigenin Inhibits NNK-Induced Focal Adhesion Kinase Activation in Pancreatic Cancer Cells

Pancreas ◽  
2012 ◽  
Vol 41 (8) ◽  
pp. 1306-1315 ◽  
Author(s):  
Hung Pham ◽  
Monica Chen ◽  
Hiroki Takahashi ◽  
Jonathan King ◽  
Howard A. Reber ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Focal Adhesion Kinase ◽  
Cancer Cells ◽  
Focal Adhesion ◽  
Kinase Activation ◽  
Pancreatic Cancer Cells

scholarly journals A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation

2013 ◽  
Vol 126 (21) ◽  
pp. 5074-5085 ◽  
Author(s):  
N. L. G. Miller ◽  
C. Lawson ◽  
E. G. Kleinschmidt ◽  
I. Tancioni ◽  
S. Uryu ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Activation
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