Translating proteomic into functional data: An high mobility group A1 (HMGA1) proteomic signature has prognostic value in breast cancer

Elisa Maurizio, Jacek R. Wis̈niewski, Yari Ciani, Angela Amato, Laura Arnoldo, Carlotta Penzo, Silvia Pegoraro, Vincenzo Giancotti, Alberto Zambelli, Silvano Piazza, Guidalberto Manfioletti, Riccardo Sgarra

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cancer is a very heterogeneous disease, and biological variability adds a further level of complexity, thus limiting the ability to identify new genes involved in cancer development. Oncogenes whose expression levels control cell aggressiveness are very useful for developing cellular models that permit differential expression screenings in isogenic contexts. HMGA1 protein has this unique property because it is a master regulator in breast cancer cells that control the transition from a nontumorigenic epithelial-like phenotype toward a highly aggressive mesenchymal-like one. The proteins extracted from HMGA1-silenced and control MDA-MB-231 cells were analyzed using label-free shotgun mass spectrometry. The differentially expressed proteins were cross-referenced with DNA microarray data obtained using the same cellular model and the overlapping genes were filtered for factors linked to poor prognosis in breast cancer gene expression meta-data sets, resulting in an HMGA1 protein signature composed of 21 members (HRS, HMGA1 reduced signature). This signature had a prognostic value (overall survival, relapse-free survival, and distant metastasis-free survival) in breast cancer. qRTPCR, Western blot, and immunohistochemistry analyses validated the link of three members of this signature (KIFC1, LRRC59, and TRIP13) with HMGA1 expression levels both in vitro and in vivo and wound healing assays demonstrated that these three proteins are involved in modulating tumor cell motility. Combining proteomic and genomic data with the aid of bioinformatic tools, our results highlight the potential involvement in neoplastic transformation of a restricted list of factors with an as-yet-unexplored role in cancer. These factors are druggable targets that could be exploited for the development of new, targeted therapeutic approaches in triple-negative breast cancer.

Original languageEnglish
Pages (from-to)109-123
Number of pages15
JournalMolecular and Cellular Proteomics
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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High Mobility Group Proteins
Proteomics
Breast Neoplasms
Neoplasms
Proteins
Overlapping Genes
Triple Negative Breast Neoplasms
Genes
Cells
Neoplasm Genes
Firearms
Oligonucleotide Array Sequence Analysis
Computational Biology
Oncogenes
Wound Healing
Cell Movement
Level control
Bioelectric potentials
Mass Spectrometry
Bioinformatics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

Translating proteomic into functional data : An high mobility group A1 (HMGA1) proteomic signature has prognostic value in breast cancer. / Maurizio, Elisa; Wis̈niewski, Jacek R.; Ciani, Yari; Amato, Angela; Arnoldo, Laura; Penzo, Carlotta; Pegoraro, Silvia; Giancotti, Vincenzo; Zambelli, Alberto; Piazza, Silvano; Manfioletti, Guidalberto; Sgarra, Riccardo.

In: Molecular and Cellular Proteomics, Vol. 15, No. 1, 01.01.2016, p. 109-123.

Research output: Contribution to journalArticle

Maurizio, E, Wis̈niewski, JR, Ciani, Y, Amato, A, Arnoldo, L, Penzo, C, Pegoraro, S, Giancotti, V, Zambelli, A, Piazza, S, Manfioletti, G & Sgarra, R 2016, 'Translating proteomic into functional data: An high mobility group A1 (HMGA1) proteomic signature has prognostic value in breast cancer', Molecular and Cellular Proteomics, vol. 15, no. 1, pp. 109-123. https://doi.org/10.1074/mcp.M115.050401
Maurizio, Elisa ; Wis̈niewski, Jacek R. ; Ciani, Yari ; Amato, Angela ; Arnoldo, Laura ; Penzo, Carlotta ; Pegoraro, Silvia ; Giancotti, Vincenzo ; Zambelli, Alberto ; Piazza, Silvano ; Manfioletti, Guidalberto ; Sgarra, Riccardo. / Translating proteomic into functional data : An high mobility group A1 (HMGA1) proteomic signature has prognostic value in breast cancer. In: Molecular and Cellular Proteomics. 2016 ; Vol. 15, No. 1. pp. 109-123.
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