PIPKIγ Regulates CCL2 Expression in Colorectal Cancer by Activating AKT-STAT3 Signaling
| Autor: | Wei Zhao, Congqi Dai, Xiaoxiao Ge, Junli Xue, Liqiong Xue, Wei Peng, Fengjuan Lin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
lcsh:Immunologic diseases. Allergy 0301 basic medicine Article Subject Colorectal cancer Immunology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Tumor Microenvironment Humans Immunology and Allergy Medicine Gene silencing STAT3 Protein kinase B Chemokine CCL2 Regulation of gene expression biology business.industry Macrophages General Medicine medicine.disease Immune checkpoint Gene Expression Regulation Neoplastic Phosphotransferases (Alcohol Group Acceptor) 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Signal transduction Colorectal Neoplasms Corrigendum lcsh:RC581-607 business Proto-Oncogene Proteins c-akt Research Article Signal Transduction |
| Zdroj: | Journal of Immunology Research, Vol 2019 (2019) Journal of Immunology Research |
| ISSN: | 2314-7156 2314-8861 |
| DOI: | 10.1155/2019/3690561 |
| Popis: | Colorectal cancer (CRC) remains the third most commonly diagnosed cancer, ranking second among the most common causes of cancer-related mortality. Immune checkpoint therapy has recently been shown to have great potential. However, only some patients respond to immune checkpoint blockade, indicating the unmet need for determining the underlying mechanism of colorectal cancer immunosuppression. In this study, we analyzed The Cancer Genome Atlas (TCGA) datasets and found that high expression of PIPKIγ positively correlated with tumor-associated macrophage infiltration. Further loss-of-function studies revealed that silencing PIPKIγ greatly reduced CCL2 expression at both the mRNA and protein levels, leading to weak chemotaxis of cancer cells to macrophages. Mechanistically, PIPKIγ facilitated PI3K-Akt-mTOR signaling pathway activation to increase STAT3 phosphorylation levels, thus triggering CCL2 transcription to enhance tumor-associated macrophage recruitment. These findings identify the PIPKIγ signaling pathway as a new actor in colorectal cancer immunosuppression and a potential therapeutic target for this common cancer. |
| Databáze: | OpenAIRE |
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