
DOI . ORG {
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Title[redir]:
CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages | Cancer Gene Therapy
Description:
We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer.
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Keywords {🔍}
cancer, cdkrap, cells, gastric, expression, macrophages, fig, tumour, tams, article, significantly, low, google, scholar, bgc, mmp, cell, cas, patients, increased, group, xenograft, tumours, ccl, coculture, polarization, mice, staining, results, number, mlike, abcam, infiltration, lin, inhibitor, data, performed, levels, analysis, wang, high, tissues, macrophage, gene, monocytes, nfκb, compared, nature, secretion, immune,
Topics {✒️}
nature portfolio privacy policy scientific research project split nature nature advertising lenti-shc53 + tams/mmp2 inhi groups chao-hui zheng chang-ming huang //portal reprints thermo fisher scientific th1/th2 cytokine profiles japan previous research reports youth research project open questions open-label selectively inhibits nf-kappab lenti-shc53 + tams/pbs groups representative haematoxylin-eosin-stained sections medical research tgf-beta tumor suppression heat-induced antigen recovery myeloid-derived suppressor cells selective nf-κb inhibitor transcription factor nf-κb chemokine receptor-specific antibodies beta-catenin signaling research progress liver-metastatic colon cancer p-nf-κb p65 permissions formalin-fixed paraffin-embedded taxane-based combination chemotherapy research illustrates cdk5rap3 inhibits nf-κb fujian medical university key laboratory research included published maps nf-κb p65 overnight tumor-induced immune suppression macrophages jia-bin wang macrophage-derived mmp2 plays tam-infiltrated tumour tissues potential binding sites higher m2 content low-expressing cdk5rap3 group social media
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headline:CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages
description:We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer.
datePublished:2022-08-23T00:00:00Z
dateModified:2022-08-23T00:00:00Z
pageStart:22
pageEnd:37
license:http://creativecommons.org/licenses/by/4.0/
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keywords:
Gastric cancer
Tumour immunology
Biomedicine
general
Gene Therapy
Gene Expression
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headline:CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages
description:We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer.
datePublished:2022-08-23T00:00:00Z
dateModified:2022-08-23T00:00:00Z
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keywords:
Gastric cancer
Tumour immunology
Biomedicine
general
Gene Therapy
Gene Expression
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