Year-end Sale % OFF 
Abstract
CXCL8 (also known as IL-8) can produce different biological effects by binding to its receptors: CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC). CXCL8 and its receptors are associated with the development of various tumor types, especially colorectal cancer and its liver metastases. In addition to promoting angiogenesis, proliferation, invasion, migration, and the survival of colorectal cancer (CRC) cells, CXCL8 and its receptors have also been known to induce the epithelial-mesenchymal transition (EMT) of CRC cells, to help them to escape host immunosurveillance as well as to enhance resistance to anoikis, which promotes the formation of circulating tumor cells (CTCs) and their colonization of distant organs. In this paper, we will review the established roles of CXCL8 signaling in CRC and discuss the possible strategies of targeting CXCL8 signaling for overcoming CRC drug resistance and cancer progression, including direct targeting of CXCL8/CXCR1/2 or indirect targeting through the inhibition of CXCL8-CXCR1/2 signaling.
Highlights
CXCL8, known as neutrophil-activating factor (NAF) and interleukin 8 (IL-8), was the first chemokine identified, and it was originally identified as a leukocyte chemoattractant [1]
The results showed that snail could activate the expression of CXCL8 directly by binding to the E3/E4 E-boxes, a CXCL8 promoter region, and regulate colon cancer stem cell activity and epithelialmesenchymal transition (EMT) in the cancer cells, which indicated that CXCL8 can interact with snail to induce EMT and promote the invasion and metastasis of colorectal cancer (CRC) cells
In the colorectal liver metastasis (CRLM) model, did Varney et al [59] find that the microvessel density in liver metastases from mice treated with a CXCR1/2 antagonist is lower but they found that the apoptosis rate of the tumor cells was higher in the CXCR1/2 antagonist-treated groups than in the control groups, which indicated that the CXCL8-CXCR1/2 signal axis promoted the growth and survival of tumor cells in the liver metastases
Summary
CXCL8, known as neutrophil-activating factor (NAF) and interleukin 8 (IL-8), was the first chemokine identified, and it was originally identified as a leukocyte chemoattractant [1]. The results showed that snail could activate the expression of CXCL8 directly by binding to the E3/E4 E-boxes, a CXCL8 promoter region, and regulate colon cancer stem cell activity and EMT in the cancer cells, which indicated that CXCL8 can interact with snail to induce EMT and promote the invasion and metastasis of CRC cells. Kobayashi et al identified several genes with significantly different microarray signals between the tumor front and the tumor center [24] Among these genes, six chemokines, including CXCL8, matrix metalloproteinase (MMP7), and EMT-related molecules, showed significant upregulation at the tumor front; the fold changes of MMP7 and EMTrelated molecules were smaller than those of CXCL8, indicating that CXCL8 was more important than MMP7 and EMT-related molecules in the process of cancer cell invasion and metastasis distance. The result that the expression of CXCL8 in cancer-adjacent tissue is higher than that in cancer center tissue seems to provide evidence to support this point of view [24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
