A multiomics analysis of S100 protein family in breast cancer

Abstract

The S100 gene family is the largest subfamily of calcium binding proteins of EF-hand type, expressed in tissue and cell-specific manner, acting both as intracellular regulators and extracellular mediators. There is a growing interest in the S100 proteins and their relationships with different cancers because of their involvement in a variety of biological events closely related to tumorigenesis and cancer progression. However, the collective role and the possible coordination of this group of proteins, as well as the functional implications of their expression in breast cancer (BC) is still poorly known. We previously reported a large-scale proteomic investigation performed on BC patients for the screening of multiple forms of S100 proteins. Present study was aimed to assess the functional correlation between protein and gene expression patterns and the prognostic values of the S100 family members in BC. By using data mining, we showed that S100 members were collectively deregulated in BC, and their elevated expression levels were correlated with shorter survival and more aggressive phenotypes of BC (basal like, HER2 enriched, ER-negative and high grading). Moreover a multi-omics functional network analysis highlighted the regulatory effects of S100 members on several cellular pathways associated with cancer and cancer progression, expecially immune response and inflammation. Interestingly, for the first time, a pathway analysis was successfully applied on different omics data (transcriptomics and proteomics) revealing a good convergence between pathways affected by S100 in BC. Our data confirm S100 members as a promising panel of biomarkers for BC prognosis.

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

“…Despite this, it is known that Ca 2+ level within the cell regulates Annexin A2 s affinity for its binding partners and cellular components such as the plasma membrane and the actin cytoskeleton [51,66,67]. Apart from Annexin A2, calcium binding proteins such as the S100 family (several of which were identified in our screen, Table S1) have been thoroughly investigated in the context of cancer, as reviewed by Bresnick et al [68] and these, along with Annexin A2, have the potential to be utilized as prognostic or therapeutic targets in breast cancer [69]. As well as successfully identifying Annexin A2 as a mediator of breast cancer cell migration and invasion, our screen has provided an extensive list of proteins potentially involved in breast cancer metastasis which require further investigation (Table S1).…”

Friend or Foe: S100 Proteins in Cancer

“…Further publications covering this connection identified S100B as a serum marker in endocrine-resistant breast cancer [86] and elevated S100B serum levels as a negative prognostic value for breast cancer [87,88]. Nevertheless, a collective expression pattern of all S100 members together might have higher prognostic value than the single proteins [82]. S100A4 is highly involved in metastasis and invasion of many different cancer types, including breast cancer [89,90].…”

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs)

“…Gels were stained with 0.2% Coomassie Brilliant Blue G-250 in 40% methanol and 10% acetic acid and de-stained in 7% methanol and 5% acetic acid. For zymography assay, aliquots of 10 μL of sera previously diluted (1 : 25) were loaded onto 7.5% polyacrylamide SDS-PAGE gel copolymerized with 0.1% gelatin, under nonreducing conditions, and run at 150 V in a Tris-glycine buffer, as described by Cancemi et al [31][32][33]. After electrophoresis, gels were incubated at room temperature for 1 h in a wash buffer (50 mM Tris-HCl pH 7.5 and 2.5% Triton X-100) to remove the SDS and then incubated for 18 h at 37°C with an activation buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, and 5 mM CaCl 2 ), to allow the activation of the gelatinases, as previously described [34,35].…”