Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp

He, Qingchun; Zhang, Guiying; Hou, Defu; Leng, Aiming; Xu, Meihua; Peng, Jie; Liu, Ting

doi:10.3892/or_00001066

Cited by 23 publications

(6 citation statements)

References 20 publications

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“…8,38 Moreover, the expression of cP-gp and sorcin were significantly correlated. 13 Regarding NHERF1 and multidrug resistance proteins, we demonstrated only an inverse trend between positive cNHERF1 expression and negative nHIF-1a expression. In previous studies, we showed an upregulation of this protein by hypoxia in breast cancer and a significant association between NHERF1 and HIF-1a in colorectal cancer.…”

Section: Discussionmentioning

confidence: 67%

“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Mangia

Caldarola

Dell'Endice

et al. 2015

Cancer Biology & Therapy

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Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na C /H C exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1a MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1a (nHIF-1a) expression (68.8% versus 31.3% respectively, P D 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1a and sorcin expression (P D 0.011; P D 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P D 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P D 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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

Mangia

Caldarola

Dell'Endice

et al. 2015

Cancer Biology & Therapy

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show abstract

“…On the strength of previous research works, three possible mechanisms that SORCIN participated in MDR are summarized. First, SORCIN might regulate the expression of P-gp (He et al, 2010;Parekh, Deng, Choudhary, Houser, & Simpkins, 2002). Second, it influenced intracellular free calcium, which linked to cell apoptosis (Maddalena et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Combination of dihydromyricetin and ondansetron strengthens antiproliferative efficiency of adriamycin in K562/ADR through downregulation of SORCIN: A new strategy of inhibiting P‐glycoprotein

Sun

Liu

Wang

et al. 2018

Journal Cellular Physiology

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Though the advancement of chemotherapy drugs alleviates the progress of cancer, long-term therapy with anticancer agents gradually leads to acquired multidrug resistance (MDR), which limits the survival outcomes in patients. It was shown that dihydromyricetin (DMY) could partly reverse MDR by suppressing P-glycoprotein (P-gp) and soluble resistance-related calcium-binding protein (SORCIN) independently. To reverse MDR more effectively, a new strategy was raised, that is, circumventing MDR by the coadministration of DMY and ondansetron (OND), a common antiemetic drug, during cancer chemotherapy. Meanwhile, the interior relation between P-gp and SORCIN was also revealed. The combination of DMY and OND strongly enhanced antiproliferative efficiency of adriamycin (ADR) because of the increasing accumulation of ADR in K562/ADR-resistant cell line. DMY could downregulate the expression of SORCIN and P-gp via the ERK/Akt pathways, whereas OND could not. In addition, it was proved that SORCIN suppressed ERK and Akt to inhibit P-gp by the silence of SORCIN, however, not vice versa. Finally, the combination of DMY, OND, and ADR led to G2/M cell cycle arrest and apoptosis via resuming P53 function and restraining relevant proteins expression. These fundamental findings provided a promising approach for further treatment of MDR.

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“…The previous studies proved that SRI acted as a pro-oncogenic and multidrug resistance gene in certain types of cancers (11)(12)(13)(14)(15). The resistance to chemotherapeutic agents is recognized as a major hurdle in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance and Prognostic Value of Human Soluble Resistance-Related Calcium-Binding Protein: A Pan-Cancer Analysis

et al. 2021

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The soluble resistance-related calcium-binding protein (sorcin, SRI) serves as the calcium-binding protein for the regulation of calcium homeostasis and multidrug resistance. Although the mounting evidence suggests a crucial role of SRI in the chemotherapeutic resistance of certain types of tumors, insights into pan-cancer analysis of SRI are unavailable. Therefore, this study aimed to probe the multifaceted properties of SRI across the 33 cancer types. The SRI expression was analyzed via The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEX) database. The SRI genomic alterations and drug sensitivity analysis were performed based on the cBioPortal and the CellMiner database. Furthermore, the correlations among the SRI expression and survival outcomes, clinical features, stemness, tumor mutation burden (TMB), microsatellite instability (MSI), and immune cells infiltration were analyzed using TCGA data. The differential analysis showed that SRI was upregulated in 25 tumor types compared with the normal tissues. Aberrant expression of SRI was able to predict survival in different cancers. Further, the most frequent alteration of SRI genomic was amplification. Moreover, the aberrant SRI expression was related to stemness score, epithelial-mesenchymal-transition (EMT)-related genes, MSI, TMB, and tumor immune microenvironment in various types of cancer. TIMER database mining further found that the SRI expression was significantly correlated with the infiltration levels of various immune cells in certain types of cancer. Intriguingly, the SRI expression was negatively correlated with drug sensitivity of fluorouracil, paclitaxel, docetaxel, and isotretinoin. Our findings highlight the predictive value of SRI in cancer and provide insights for illustrating the role of SRI in tumorigenesis and drug resistance.

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Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp

Cited by 23 publications

References 20 publications

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

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

Combination of dihydromyricetin and ondansetron strengthens antiproliferative efficiency of adriamycin in K562/ADR through downregulation of SORCIN: A new strategy of inhibiting P‐glycoprotein

Clinical Significance and Prognostic Value of Human Soluble Resistance-Related Calcium-Binding Protein: A Pan-Cancer Analysis

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