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An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer

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Abstract

Chronic inflammation is a major factor in tumor growth and progression. Cancer cells secrete C-X-C chemokine ligand 8 (CXCL8) along with its receptor C-X-C chemokine receptor 1 (CXCR1) and chemokine receptor 2 (CXCR2). It plays a significant role in the activation and trafficking of inflammatory mediators, tumor proliferation and interferes in breast cancer development by controlling cell adhesion, proliferation, migration, and metastasis. This axis also plays a significant role in driving different cancers and melanomas, including breast cancer progression, by controlling stem cell masses. Few small-molecule CXCR1/2 inhibitors and CXCL8 releasing inhibitors have been identified in the past two decades that bind these receptors in their inactive forms and blocks their signaling as well as the biological activities associated with inflammation. Inhibitors of certain inflammatory molecules are projected to be more efficient in different inflammatory diseases. Preclinical trials indicate that patients may be benefitted from combined treatment with targeted drugs, chemotherapies, and immunotherapies. Thus, targeting the CXCL8-CXCR1/2 signaling axis in breast cancer could be a promising approach for its therapeutics. This review examines the roles of the CXCL8-CXCR1/2 signaling axis and how it is implicated in the tumor microenvironment in breast cancer. In addition, we also discuss the potential role of the CXCL8-CXCR1/2 axis in targeted therapeutics for breast cancer.

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Fig. 1

Copyright 2016 Elsevier). CXCL8 interacts with G protein-coupled receptors (GPCRs), such as CXCR1 or CXCR2, leading to G protein activation at the cellular level. Heterotrimeric Ga and bg subunits activate the major effectors PLC and PI3K to induce phosphorylation of PKC and Akt, respectively. The two signaling pathways have been shown to activate transcription factors involved in tumor cell survival, angiogenesis, and migration. CXCL8 also promotes cell proliferation, survival, motility, and invasion by activating non-receptor tyrosine kinases (e.g., Src and FAK) and members of the RhoGTPase family. Cell proliferation and survival are aided by an activated Raf-1/MAP/Erk signaling cascade. Dashed arrows show unconfirmed pathways implicated in the CXCL8 signaling axis

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Authors and Affiliations

  1. School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India

    Amaresh Mishra & Vishwas Tripathi

  2. Department of Environment & Aquatic Biology, ABEx Bio-research Center, Azampur, Dhaka, 1230, Bangladesh

    Kamrul Hassan Suman

  3. Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences and Research University, Govt of NCT of Delhi, New Delhi, 110017, India

    Nisha Nair

  4. School of Allied Health Sciences, Delhi Pharmaceutical Sciences and Research University, Govt of NCT of Delhi, New Delhi, 110017, India

    Jaseela Majeed

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  1. Amaresh Mishra
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  2. Kamrul Hassan Suman
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  4. Jaseela Majeed
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  5. Vishwas Tripathi
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AM, and NN conducted the literature search and did writing. KHS contributed to writing. JM, and VT conceptualized the ideas and contributed to writing and preparing the final version of the manuscript.

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Correspondence to Vishwas Tripathi.

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Mishra, A., Suman, K.H., Nair, N. et al. An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer. Mol Biol Rep 48, 6551–6561 (2021). https://doi.org/10.1007/s11033-021-06648-8

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  • DOI: https://doi.org/10.1007/s11033-021-06648-8

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