Data from HSulf-1 Modulates FGF2- and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells

التفاصيل البيبلوغرافية
العنوان: Data from HSulf-1 Modulates FGF2- and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells
المؤلفون: Viji Shridhar, Alfonso Baldi, Jeremy Chien, Wilma Lingle, Robert J. Linhardt, Bo Yang, Kaustubh Datta, Bruno Vincenzi, Laura Lorenzon, Pasquale Mellone, Peng Liu, Ashwani Khurana
بيانات النشر: American Association for Cancer Research (AACR), 2023.
سنة النشر: 2023
الوصف: HSulf-1 modulates the sulfation states of heparan sulfate proteoglycans critical for heparin binding growth factor signaling. In the present study, we show that HSulf-1 is transcriptionally deregulated under hypoxia in breast cancer cell lines. Knockdown of HIF-1α rescued HSulf-1 downregulation imposed by hypoxia, both at the RNA and protein levels. Chromatin immunoprecipitation with HIF-1α and HIF-2α antibodies confirmed recruitment of HIF-α proteins to the two functional hypoxia-responsive elements on the native HSulf-1 promoter. HSulf-1 depletion in breast cancer cells resulted in an increased and sustained bFGF2 (basic fibroblast growth factor) signaling and promoted cell migration and invasion under hypoxic conditions. In addition, FGFR2 (fibroblast growth factor receptor 2) depletion in HSulf-1–silenced breast cancer cells attenuated hypoxia-mediated cell invasion. Immunohistochemical analysis of 53 invasive ductal carcinomas and their autologous metastatic lesions revealed an inverse correlation for the expression of HSulf-1 to CAIX in both the primary tumors (P ≥ 0.0198) and metastatic lesions (P ≥ 0.0067), respectively, by χ2 test. Finally, HSulf-1 expression levels in breast tumors by RNA in situ hybridization showed that high HSulf-1 expression is associated with increased disease-free and overall survival (P ≥ 0.03 and P ≥ 0.0001, respectively). Collectively, these results reveal an important link between loss of HSulf-1 under hypoxic microenvironment and increased growth factor signaling, cell migration, and invasion. Cancer Res; 71(6); 2152–61. ©2011 AACR.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b5a82f9a9b827faa3bbe1f093eb5cc30Test
https://doi.org/10.1158/0008-5472.c.6502983.v1Test
حقوق: OPEN
رقم الانضمام: edsair.doi...........b5a82f9a9b827faa3bbe1f093eb5cc30
قاعدة البيانات: OpenAIRE