2. Academic Validation
  3. CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway

CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway

  • Biol Direct. 2022 Nov 25;17(1):34. doi: 10.1186/s13062-022-00348-4.
Changhua Zhuo 1 2 3,  Qiang Ruan 4,  Xiangqian Zhao 5,  Yangkun Shen 6,  Ruirong Lin 7 4 8
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People's Republic of China. [email protected].
  • 2 Fuzhou University, College of Chemistry, Fuzhou, 350108, People's Republic of China. [email protected].
  • 3 Fujian Key Laboratory of Translational Cancer Medicine and Fujian Provincial Key Laboratory of Tumor Biotherapy, Fuzhou, Fujian, 350014, People's Republic of China. [email protected].
  • 4 Fuzhou University, College of Chemistry, Fuzhou, 350108, People's Republic of China.
  • 5 Fujian Normal University Qishan Campus, College of Life Science, Biomedical Research Center of South China, Fuzhou, 350117, People's Republic of China.
  • 6 Fujian Normal University Qishan Campus, College of Life Science, Biomedical Research Center of South China, Fuzhou, 350117, People's Republic of China. [email protected].
  • 7 Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People's Republic of China.
  • 8 Fujian Key Laboratory of Translational Cancer Medicine and Fujian Provincial Key Laboratory of Tumor Biotherapy, Fuzhou, Fujian, 350014, People's Republic of China.
PMID: 36434686 DOI: 10.1186/s13062-022-00348-4
Abstract

Background: The upregulated expression of CXCL1 has been validated in colorectal Cancer patients. As a potential biotherapeutic target for colorectal Cancer, the mechanism by which CXCL1 affects the development of colorectal Cancer is not clear.

Methods: Expression data of CXCL1 in colorectal Cancer were obtained from the GEO database and verified using the GEPIA database and the TIMER 2.0 database. Knockout and overexpression of CXCL1 in colorectal Cancer cells by CRISPR/Cas and "Sleeping Beauty" transposon-mediated gene editing techniques. Cell biological function was demonstrated by CCK-8, transwell chamber and Colony formation assay. RT-qPCR and Western Blot assays measured RNA and protein expression. Protein localization and expression were measured by immunohistochemistry and immunofluorescence.

Results: Bioinformatics analysis showed significant overexpression of CXCL1 in the colorectal Cancer tissues compared to normal human tissues, and identified CXCL1 as a potential therapeutic target for colorectal Cancer. We demonstrate that CXCL1 promotes the proliferation and migration of colon Cancer cells and has a facilitative effect on tumor angiogenesis. Furthermore, CXCL1 elevation promoted the migration of M2-tumor associated macrophages (TAMs) while disrupting the aggregation of CD4+ and CD8+ T cells at tumor sites. Mechanistic studies suggested that CXCL1 activates the NF-κB pathway. In the in vivo colon Cancer transplantation tumor model, treatment with the P300 inhibitor C646 significantly inhibited the growth of CXCL1-overexpressing colon Cancer.

Conclusion: CXCL1 promotes colon Cancer development through activation of NF-κB/P300, and that CXCL1-based therapy is a potential novel strategy to prevent colon Cancer development.

Keywords

C646; CXCL1; Colon cancer; NF-κB; P300.

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