HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells

Resmini, Giulia; Rizzo, Serena; Franchin, Cinzia; Zanin, Rossella; Penzo, Carlotta; Pegoraro, Silvia; Ciani, Yari; Piazza, Silvano; Arrigoni, Giorgio; Sgarra, Riccardo; Manfioletti, Guidalberto

doi:10.1038/s41598-017-11409-4

Cited by 28 publications

(22 citation statements)

References 32 publications

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“…PLAU, urokinase-type plasminogen activator protease (uPA), is a secreted factor that binds to the outer cell surface, remodels the extracellular matrix, and then allows cells to move inside tissues. 53,54 Furthermore, PLAU is overexpressed in many cancer cells and is important for cancer cell metastatic spread. 28,55 MMP9 is involved in the breakdown of the extracellular matrix and promotes cancer cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression

et al. 2019

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The prognosis for patients with bladder cancer (BCa) with lymph node (LN) metastasis is poor, and it is not improved by current treatments. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including BCa. However, the role of Differentiation antagonizing non-protein coding RNA (DANCR) in BCa LN metastasis remains unclear. In this study, we discover that DANCR was significantly upregulated in BCa tissues and cases with LN metastasis. DANCR expression was positively correlated with LN metastasis status, tumor stage, histological grade, and poor patient prognosis. Functional assays demonstrated that DANCR promoted BCa cell migration, invasion, and proliferation in vitro and enhanced tumor LN metastasis and growth in vivo. Mechanistic investigations revealed that DANCR activated IL-11-STAT3 signaling and increased cyclin D1 and PLAU expression via guiding leucine-rich pentatricopeptide repeat containing (LRPPRC) to stabilize mRNA. Moreover, oncogenesis facilitated by DANCR was attenuated by anti-IL-11 antibody or a STAT3 inhibitor (BP-1-102). In conclusion, our findings indicate that DANCR induces BCa LN metastasis and proliferation via an LRPPRC-mediated mRNA stabilization mechanism. DANCR may serve as a multi-potency target for clinical intervention in LN-metastatic BCa.

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Section: Discussionmentioning

confidence: 99%

DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression

et al. 2019

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“…Recently, the use of gene expression analysis gave rise to different hypothesis on mechanisms used by HMGA1 in tumorigenesis. These studies have suggested the involvement of different signaling pathways such as the Ras/ERK, Wnt/b catenin, Notch, and Hippo signaling pathways in the action of HMGA1 (38,(40)(41)(42). However, most of these studies focused on the intracellular role of HMGA1 in cancer.…”

Section: Discussionmentioning

confidence: 99%

Extracellular HMGA1 Promotes Tumor Invasion and Metastasis in Triple-Negative Breast Cancer

Méndez¹,

Peg

Salvans³

et al. 2018

Clinical Cancer Research

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The study of the cancer secretome suggests that a fraction of the intracellular proteome could play unanticipated roles in the extracellular space during tumorigenesis. A project aimed at investigating the invasive secretome led us to study the alternative extracellular function of the nuclear protein high mobility group A1 (HMGA1) in breast cancer invasion and metastasis. Antibodies against HMGA1 were tested in signaling, adhesion, migration, invasion, and metastasis assays using breast cancer cell lines and xenograft models. Fluorescence microscopy was used to determine the subcellular localization of HMGA1 in cell lines, xenograft, and patient-derived xenograft models. A cohort of triple-negative breast cancer (TNBC) patients was used to study the correlation between subcellular localization of HMGA1 and the incidence of metastasis. Our data show that treatment of invasive cells with HMGA1-blocking antibodies in the extracellular space impairs their migration and invasion abilities. We also prove that extracellular HMGA1 (eHMGA1) becomes a ligand for the Advanced glycosylation end product-specific receptor (RAGE), inducing pERK signaling and increasing migration and invasion. Using the cytoplasmic localization of HMGA1 as a surrogate marker of secretion, we showed that eHMGA1 correlates with the incidence of metastasis in a cohort of TNBC patients. Furthermore, we show that HMGA1 is enriched in the cytoplasm of tumor cells at the invasive front of primary tumors and in metastatic lesions in xenograft models. Our results strongly suggest that eHMGA1 could become a novel drug target in metastatic TNBC and a biomarker predicting the onset of distant metastasis.

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“…To further clean the sample from the detergent present in the extraction buffer, protein pellets were loaded into a pre-cast 4–12% SDS gel and the electrophoretic run was stopped as soon as the protein extracts entered the running gel. They were then excised from the gels as single, narrow bands, and in situ digestion and peptide extraction were performed according to Resmini et al (2017). The resulting peptide solution was desalted on a C18 solid-phase extraction cartridge and 1 μg of each sample was analyzed by LC–MS/MS to check the digestion efficiency (details of the instruments and instrumental methods are given in the following section).…”

Section: Methodsmentioning

confidence: 99%

Protein Profiling of Arabidopsis Roots Treated With Humic Substances: Insights Into the Metabolic and Interactome Networks

et al. 2018

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Background and Aim: Humic substances (HSs) influence the chemical and physical properties of the soil, and are also known to affect plant physiology and nutrient uptake. This study aimed to elucidate plant metabolic pathways and physiological processes influenced by HS activity.Methods: Arabidopsis roots were treated with HS for 8 h. Quantitative mass spectrometry-based proteomics analysis of root proteins was performed using the iTRAQ (Isobaric Tag for Relative and Absolute Quantification) technique. Out of 902 protein families identified and quantified for HS treated vs. untreated roots, 92 proteins had different relative content. Bioinformatic tools such as STRING, KEGG, IIS and Cytoscape were used to interpret the biological function, pathway analysis and visualization of network amongst the identified proteins.Results: From this analysis it was possible to evaluate that all of the identified proteins were functionally classified into several categories, mainly redox homeostasis, response to inorganic substances, energy metabolism, protein synthesis, cell trafficking, and division.Conclusion: In the present study an overview of the metabolic pathways most modified by HS biological activity is provided. Activation of enzymes of the glycolytic pathway and up regulation of ribosomal protein indicated a stimulation in energy metabolism and protein synthesis. Regulation of the enzymes involved in redox homeostasis suggest a pivotal role of reactive oxygen species in the signaling and modulation of HS-induced responses.

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HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells

Cited by 28 publications

References 32 publications

DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression

DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression

Extracellular HMGA1 Promotes Tumor Invasion and Metastasis in Triple-Negative Breast Cancer

Protein Profiling of Arabidopsis Roots Treated With Humic Substances: Insights Into the Metabolic and Interactome Networks

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