Serglycin promotes breast cancer cell aggressiveness: Induction of epithelial to mesenchymal transition, proteolytic activity and IL-8 signaling

Matrix Biology : Journal of the International Society for Matrix Biology
Panagiotis BourisAchilleas D Theocharis

Abstract

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 α (ERα)-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 ERα-negative breast cancer cells and tumors. Notably, serglycin regulated the secretion of...Continue Reading

Citations

Mar 26, 2019·The FEBS Journal·Achilleas D TheocharisNikos K Karamanos
Mar 21, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Sep 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hossam Taha MohamedStéphane Brézillon
Aug 23, 2020·International Journal of Molecular Sciences·Jinfen WeiHongli Du
Oct 7, 2020·The Journal of Biological Chemistry·Carolyn G Chen, Renato V Iozzo
Jan 9, 2021·Frontiers in Immunology·Shahid HussainRamesh K Ganju
Dec 15, 2020·Journal of Clinical Laboratory Analysis·Layi WangXiajun Wang
Apr 17, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Jan 18, 2021·The Journal of Biological Chemistry·Carolyn G Chen, Renato V Iozzo
Feb 20, 2021·The FEBS Journal·Nikos K KaramanosMaurizio Onisto
Jun 21, 2021·Cancer Treatment and Research Communications·Fares Hezam Al-OstootShaukath Ara Khanum
Aug 15, 2021·Trends in Molecular Medicine·Nikos K KaramanosIsrael Vlodavsky
Aug 10, 2021·World Journal of Clinical Oncology·Yun Zhu, Annie Lai Man Cheung
Sep 12, 2018·Chemical Reviews·Nikos K KaramanosRenato V Iozzo
Dec 8, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Atanaska I DonchevaSvein O Kolset

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