Upregulation of soluble resistance-related calcium-binding protein (sorcin) in gastric cancer

Abstract

The aim of this paper was to identify novel proteins involved in the development of gastric cancer (GC). Isobaric tags for relative and absolute quantification (iTRAQ) analysis was adopted to separate the differentially expressed proteins between normal gastric epithelial cell line GES-1 and GC cell line SGC7901. Western blotting was utilized to validate the increased expression of sorcin in SGC7901; immunohistochemistry was performed to investigate its relationship with clinicopathological features of GC. Twelve differential proteins were identified. Seven proteins were found to be significantly upregulated (≥two-fold), while five proteins were markedly downregulated (≤0.5-fold), in SGC7901 cells. Sorcin was detected by this proteomic approach with a 5.4-fold upregulation in SGC7901. Western blotting and immunohistochemistry confirmed the overexpression of sorcin in GC. Immunohistochemistry showed us that sorcin was overexpressed in 55 samples of GC tissue (55/85, 64.71%) and was related closely to the depth of invasion, TNM stage, and lymph node metastasis of GC (P<0.05). The development of GC is regulated by multiple genes. Sorcin will be a novel molecular biomarker for the diagnosis, treatment, and prognosis of GC.

Mitochondrial Chaperone Trap1 and the Calcium Binding Protein Sorcin Interact and Protect Cells against Apoptosis Induced by Antiblastic Agents

“…Sorcin has been implicated in chemoresistance and cancer as well. In fact, high levels of this protein have been reported in cancer cell lines and vincristine-resistant gastric cancer cell lines (16)(17)(18). Furthermore, Sorcin expression might be responsible for drug resistance and poor prognosis in non-small cell lung tumors (19,20).…”

“…Both these proteins have previously been implicated in chemoresistance, in part due to their ability to modulate Ca 2+ levels. Other reports suggest a correlation between Sorcin and the multidrug-resistant MDR1/P-glycoprotein: it has been shown that the knockdown of Sorcin induces the upregulation of MDR1 in HeLa cells (15); by contrast, a direct correlation between Sorcin and multidrug resistance overexpression has also been reported in human gastric cancer cell lines and vincristine-resistant gastric cancer cells (16)(17)(18). Finally, recent studies aimed at evaluating changes in gene expression profile in oral squamous cell carcinoma and non-small cell lung cancer identified a cDNA homologous to Sorcin expressed only in tumors, apparently responsible for drug resistance and poor prognosis (19,20).…”

The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy

“…[7][8][9][10][11][12] Furthermore, the soluble resistance-related calcium binding protein (sorcin) is involved in the up-regulation of P-gp in GC cell lines and thus in the development of the MDR phenotype. [13][14][15][16] Hypoxia, a common characteristic of many tumors, has also been described as a crucial player in the drug resistance mechanisms. [17][18][19] In particular, hypoxia-inducible factor-1a (HIF-1a) is involved in the tumor response to cellular hypoxia through the transcriptional regulation of a large number of hypoxia-related genes, including MDR genes.…”

Proteomics-based analysis of differentially expressed proteins in the CXCR1-knockdown gastric carcinoma MKN45 cell line and its parental cell

“…Sorcin was first identified in a vincristine-resistant Chinese hamster lung cell line, and was later demonstrated to be overexpressed in several tumor cell types [33][34][35] and many multidrug resistance (MDR) cell lines [36,37]. As to the role of sorcin overexpression in human gastric cancer and the underlying mechanisms of sorcin in drug resistance, Deng et al [38] argued that the overexpression of sorcin was related to the depth of invasion, TNM stage, and lymph node metastasis, which suggested that sorcin may contribute to progression and metastasis of gastric carcinoma and sorcin plays an important role in the development of gastric carcinoma probably by regulating the apoptotic pathways in gastric carcinoma cells, which was further elucidated in another paper [39]. It was reported that sorcin was identified as a new binding partner of TRAP1 (a mitochondrial chaperone HSP75) in MDR of human colorectal carcinoma cells, indicating that the cytoprotective function of sorcin may be involved in TRAP1-associated signaling pathway, which was coincident with the result of Maddalena et al [36] They found that RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/ BiP, and then triggered apoptosis through the mitochondrial pathway, which established that human colorectal cancer cells overexpressing sorcin as an adaptive mechanism to escape apoptosis triggered by chemotherapeutic agents, while He et al [40] argued that regulation of P-glycoprotein (P-gp) might be one of the mechanisms of sorcin-mediated MDR, for they found that overexpression of sorcin up-regulated the expression of P-gp, and P-gp inhibitor verapamil partially reversed the sorcin-mediated MDR in SGC7901 cell.…”