LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes
- Authors
- Park, Geun-Soo; Kim, Jae-Hong
- Issue Date
- 9월-2015
- Publisher
- KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- Keywords
- beast cancer; BLT2; ICAM-1; LPS; MyD88
- Citation
- MOLECULES AND CELLS, v.38, no.9, pp.821 - 828
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- MOLECULES AND CELLS
- Volume
- 38
- Number
- 9
- Start Page
- 821
- End Page
- 828
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/92649
- DOI
- 10.14348/molcells.2015.0174
- ISSN
- 1016-8478
- Abstract
- Monocytes are the major inflammatory cells that infiltrate most solid tumors in humans. The interaction of tumor cells with infiltrating monocytes and their adhesion to these monocytes play a significant role in altering the tumor to become more aggressive. Recently, exposure to lipopolysaccharide (LPS) was suggested to promote cancer cell adhesion to monocytes; however, little is known about the details of the signaling mechanism involved in this process. In this study, we found that LPS up-regulates ICAM-1 expression in MDA-MB-231 breast cancer cells, which facilitates their adhesion to THP-1 monocytes. In addition, we analyzed the signaling mechanism underlying the up-regulation of ICAM-1 and found that the siRNA-mediated depletion of BLT2 markedly suppressed the LPS-induced expression of ICAM-1 in MDA-MB-231 cells and the subsequent adhesion of these cells to THP-1 monocytes. Moreover, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies downstream of LPS/TLR4 and upstream of BLT2 and that this 'MyD88BLT2' cascade mediates ERK activation and subsequent ICAM-1 expression, which is critical for the adhesion of MDA-MB-231 cells to THP-1 monocytes. Taken together, our results demonstrate for the first time that LPS up-regulates ICAM-1 expression in breast cancer cells via a MyD88-BLT2-ERK-linked signaling cascade, leading to the increased adhesion of breast cancer cells to monocytes.
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