• Patchliner

    Most versatile automated patch clamp system on the market
  • Patchliner

    In-house production and QC of consumables
  • Patchliner

    More than 10 years experience in assay design and support
  • Patchliner

    All features & benefits of manual patch clamp
  • Patchliner

    More than 100 Patchliners sold worldwide

2019 - GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner

icon pl   Patchliner publication in Gut (2019)

Authors:
Jiang S.H., Zhu L.L., Zhang M., Li R.K., Yang Q., Yan J.Y., Zhang C., Yang J.Y., Dong F.Y., Dai M., Hu L.P., Li J., Li Q., Wang Y.H., Yang X.M., Zhang Y.L., Nie H.Z., Zhu L., Zhang X.L., Tian G.A., Zhang X.X., Cao X.Y., Tao L.Y., Huang S., Jiang Y.S., Hua R., Qian Luo K., Gu J.R., Sun Y.W., Hou S., Zhang Z.G.

Journal:
Gut (2019): doi: 10.1136/gutjnl-2018-317479


BACKGROUND AND AIMS:
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis.

METHODS:
The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism.

RESULTS:
GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression.

CONCLUSIONS:
Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.


Download here

Back to Overview

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok