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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
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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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         Gastric cancer
         Tumour immunology
         Biomedicine
         general
         Gene Therapy
         Gene Expression
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            name:Fujian Medical University Union Hospital
            address:
               name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
               type:PostalAddress
            type:Organization
            name:Fujian Medical University
            address:
               name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
               type:PostalAddress
            type:Organization
            name:Fujian Medical University
            address:
               name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Chang-Ming Huang
      url:http://orcid.org/0000-0002-0019-885X
      affiliation:
            name:Fujian Medical University Union Hospital
            address:
               name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
               type:PostalAddress
            type:Organization
            name:Fujian Medical University
            address:
               name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
               type:PostalAddress
            type:Organization
            name:Fujian Medical University
            address:
               name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China
      name:Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
      name:Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
      name:Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University, Fuzhou, China

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