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Serglycin promotes ...
Serglycin promotes breast cancer cell aggressiveness : Induction of epithelial to mesenchymal transition, proteolytic activity and IL-8 signaling
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- Bouris, Panagiotis (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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- Manou, Dimitra (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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- Sopaki-Valalaki, Anastasia (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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- Kolokotroni, Anthi (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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- Moustakas, Aristidis (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Kapoor, Aastha (author)
- Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Canc Cell Biol & Signaling Program, Philadelphia, PA 19107 USA
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- Iozzo, Renato V. (author)
- Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Canc Cell Biol & Signaling Program, Philadelphia, PA 19107 USA
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- Karamanos, Nikos K. (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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- Theocharis, Achilleas D. (author)
- Univ Patras, Dept Chem, Biochem Biochem Anal & Matrix Pathobiol Res Grp, Lab Biochem, GR-26110 Patras, Greece
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(creator_code:org_t)
- ELSEVIER SCIENCE BV, 2018
- 2018
- English.
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In: Matrix Biology. - : ELSEVIER SCIENCE BV. - 0945-053X .- 1569-1802. ; 74, s. 35-51
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Serglycin is an intracellular proteoglycan that is expressed and constitutively secreted by numerous malignant cells, especially prominent in the highly-invasive, triple-negative MDA-MB-231 breast carcinoma cells. Notably, de novo expression of serglycin in low aggressive estrogen receptor alpha (ER alpha)-positive MCF7 breast cancer cells promotes an aggressive phenotype. In this study, we discovered that serglycin promoted epithelial to mesenchymal transition (EMT) in MCF7 cells as shown by increased expression of mesenchymal markers vimentin, fibronectin and EMT-related transcription factor Snail2. These phenotypic traits were also associated with the development of drug resistance toward various chemotherapy agents and induction of their proteolytic potential as shown by the increased expression of matrix metalloproteinases, including MMP-1, MMP-2, MMP-9, MT1-MMP and up-regulation of urokinase-type plasminogen activator. Knockdown of serglycin markedly reduced the expression of these proteolytic enzymes in MDA-MB-231 cells. In addition, serglycin expression was closely linked to a pro-inflammatory gene signature including the chemokine IL-8 in ER alpha-negative breast cancer cells and tumors. Notably, serglycin regulated the secretion of IL-8 in breast cancer cells independently of their ER alpha status and promoted their proliferation, migration and invasion by triggering IL-8/CXCR2 downstream signaling cascades including PI3K, Src and Rac activation. Thus, serglycin promotes the establishment of a pro-inflammatory milieu in breast cancer cells that evokes an invasive mesenchymal phenotype via autocrine activation of IL-8/CXCR2 signaling axis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Proteoglycans
- Serglycin
- Interleukin-8
- Breast cancer
- Signaling
Publication and Content Type
- ref (subject category)
- art (subject category)
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