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CXCL6: A potential therapeutic target for inflammation and cancer

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A Correction to this article was published on 26 October 2023

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Abstract

Chemokines were originally defined as cytokines that affect the movement of immune cells. In recent years, due to the increasing importance of immune cells in the tumor microenvironment (TME), the role of chemokines has changed from a single "chemotactic agent" to a key factor that can regulate TME and affect the tumor phenotype. CXCL6, also known as granulocyte chemoattractant protein-2 (GCP-2), can recruit neutrophils to complete non-specific immunity in the process of inflammation. Cancer-related genes and interleukin family can promote the abnormal secretion of CXCL6, which promotes tumor growth, metastasis, epithelial mesenchymal transformation (EMT) and angiogenesis in the TME. CXCL6 also has a role in promoting fibrosis and tissue damage repair. In this review, we focus on the regulatory network affecting CXCL6 expression, its role in the progress of inflammation and how it affects tumorigenesis and progression based on the TME, in an attempt to provide a potential target for the treatment of diseases such as inflammation and cancer.

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Abbreviations

TME:

Tumor microenvironment

GCP-2:

Granulocyte chemoattractant protein-2

EMT:

Epithelial mesenchymal transformation

HCC:

Hepatocellular carcinoma

PTX:

Pertussis toxin

ACKR:

Atypical chemokine receptors

ELR:

Glutamic acid–leucine–arginine

RA:

Rheumatoid arthritis

NETs:

Neutrophil extracellular traps

FLSs:

Fibroblast-like synoviocytes

FLS-OA:

Osteoarthritic fibroblast-like synoviocytes

LPS:

Lipopolysaccharide

TNF-α:

Tumor necrosis factor-α

CAP1:

Cyclase-associated protein 1

HDAC:

Histone deacetylase

IL-1β:

Interleukin-1β

DN:

Diabetes nephropathy

AKI:

Acute renal injury

ARPCs:

Adult renal progenitor cells

PPARα:

Peroxisome proliferator-activated receptor α

HRSV:

Human respiratory syncytial virus

PITX2:

Paired-like homeodomain transcription factor 2

GC:

Glucocorticoid

IBD:

Inflammatory bowel disease

AD:

Atopic dermatitis

T1R:

Type 1 response

BPH:

Benign prostatic hyperplasia

TSPAN12:

Tetraspanin 12

RNF152:

Ring finger protein 152

PAI-1:

Plasminogen activator inhibitor-1

CLCF1:

Cardiotrophin-like cytokine factor 1

CAF:

Cancer-associated fibroblasts

NSCLC:

Non-small cell lung cancer

Th17:

T cell helper 17

AML:

Acute myeloid leukemia

VEGF:

Vascular endothelial growth factor

TAM:

Tumor-associated macrophages

ESCC:

Esophageal squamous cell carcinoma

PD-L1:

Programmed cell death ligand 1

HIF-α:

Hypoxia-inducible factor-1α

TANs:

Tumor-associated neutrophils

BRD7:

Bromodomain-containing protein 7

SSc:

Systemic sclerosis

HUVECs:

Human umbilical vein endothelial cells

Fli1:

Friend leukemia virus integration 1

HGF:

Hepatocyte growth factor

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Acknowledgements

We are indebted to all individuals who participated in or helped with this research project.

Funding

This work was supported by funds from the National Natural Science Foundation of China (No. 82174023) and the Three-Year Action Plan for Shanghai TCM Development and Inheritance Program (ZY(2021-2023)-0401).

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  1. Chun-Lan Dai and Hong-Xuan Yang contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Chun-Lan Dai, Hong-Xuan Yang, Qiu-Ping Liu & Hong Zhang

  2. School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool, UK

    Khalid Rahman

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Contributions

HZ conceptualized the study. C-LD, H-XY and Y-QD wrote the original draft of the manuscript. C-LD, H-XY, Y-QD and HZ wrote, reviewed and edited the manuscript. KR and HZ contributed to verification and recommendation. All authors contributed to the article and approved the submitted version.

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Correspondence to Hong Zhang.

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Dai, CL., Yang, HX., Liu, QP. et al. CXCL6: A potential therapeutic target for inflammation and cancer. Clin Exp Med 23, 4413–4427 (2023). https://doi.org/10.1007/s10238-023-01152-8

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