RRC ID 49319
Author Resmini G, Rizzo S, Franchin C, Zanin R, Penzo C, Pegoraro S, Ciani Y, Piazza S, Arrigoni G, Sgarra R, Manfioletti G.
Title HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells.
Journal Sci Rep
Abstract Cancer cells secrete proteins that modify the extracellular environment acting as autocrine and paracrine stimulatory factors and have a relevant role in cancer progression. The HMGA1 oncofetal protein has a prominent role in controlling the expression of an articulated set of genes involved in various aspect of cancer cell transformation. However, little is known about its role in influencing the secretome of cancer cells. Performing an iTRAQ LC-MS/MS screening for the identification of secreted proteins, in an inducible model of HMGA1 silencing in breast cancer cells, we found that HMGA1 has a profound impact on cancer cell secretome. We demonstrated that the pool of HMGA1-linked secreted proteins has pro-migratory and pro-invasive stimulatory roles. From an inspection of the HMGA1-dependent secreted factors it turned out that HMGA1 influences the presence in the extra cellular milieu of key components of the Plasminogen activation system (PLAU, SERPINE1, and PLAUR) that has a prominent role in promoting metastasis, and that HMGA1 has a direct role in regulating the transcription of two of them, i.e. PLAU and SERPINE1. The ability of HMGA1 to regulate the plasminogen activator system may constitute an important mechanism by which HMGA1 promotes cancer progression.
Volume 7(1)
Pages 11768
Published 2017-9-18
DOI 10.1038/s41598-017-11409-4
PII 10.1038/s41598-017-11409-4
PMID 28924209
PMC PMC5603555
MeSH Cell Line, Tumor Cell Transformation, Neoplastic* Female Gene Expression Regulation, Neoplastic* HEK293 Cells HMGA Proteins / metabolism* Humans Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Plasminogen / genetics Plasminogen / metabolism* Triple Negative Breast Neoplasms / genetics Triple Negative Breast Neoplasms / metabolism* Triple Negative Breast Neoplasms / pathology
IF 3.998
Times Cited 15
DNA material pGL4-phPLAU (RDB07487) pGL4-phSERPINE1(PAI-1) (RDB07461).