Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells

Huang, Zhengxiang; Fan, Guojun; Wang, Dongliang

doi:10.3892/ol.2017.5931

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…However, alternative Ca 2+ -sensing functions have also been proposed for calbindin, with the identification of several binding partners ( 66 , 67 ). While the physiological relevance of calbindin-binding partners remains unclear ( 66 , 67 ), recent in vitro studies support an oncogenic role for the canonical isoform of calbindin, with one study implicating binding to the E3 ubiquitin ligase MDM2 ( 60 , 68 , 69 ). Moreover, chimeric HERVH-CALB1 transcripts detected in human ES cells and preimplantation embryos raise the possibility that ectopic expression of calbindin, particularly in the epiblast as detected here and in a recent report ( 28 ), may represent an exaptation event that contributes to normal human embryo development.…”

Section: Discussionmentioning

confidence: 99%

Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin

Attig¹,

Pape²,

Doglio³

et al. 2023

Journal of Clinical Investigation

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Increased levels and diversity of human endogenous retrovirus (HERV) transcription characterize most cancer types and are linked with disease outcomes. However, the underlying processes are incompletely understood. Here, we show that elevated transcription of HERVH proviruses predicted survival of lung squamous cell carcinoma (LUSC) and identified an isoform of CALB1 , encoding calbindin, ectopically driven by an upstream HERVH provirus under the control of KLF5, as the mediator of this effect. HERVH - CALB1 expression was initiated in preinvasive lesions and associated with their progression. Calbindin loss in LUSC cell lines impaired in vitro and in vivo growth and triggered senescence, consistent with a protumor effect. However, calbindin also directly controlled the senescence-associated secretory phenotype (SASP), marked by secretion of CXCL8 and other neutrophil chemoattractants. In established carcinomas, CALB1 -negative cancer cells became the dominant source of CXCL8, correlating with neutrophil infiltration and worse prognosis. Thus, HERVH - CALB1 expression in LUSC may display antagonistic pleiotropy, whereby the benefits of escaping senescence early during cancer initiation and clonal competition were offset by the prevention of SASP and protumor inflammation at later stages.

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Section: Discussionmentioning

confidence: 99%

Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin

Attig¹,

Pape²,

Doglio³

et al. 2023

Journal of Clinical Investigation

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“…CALB1 is overexpressed in nonsmall cell lung cancer (NSCLC) tissues, and has a significant connection with lymph node metastasis and prediction of worse survival ( 56 ). In osteosarcoma, the downregulation of CALB1 gene expression resulted in reduced cell proliferation and cell clonal formation ( 57 ). In this study, CALB1 was verified to be an independent risk factor for prognosis.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis

Yang

Lu²,

Peng³

et al. 2022

Front. Immunol.

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BackgroundColon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC.MethodsThe Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated.ResultsCALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC.ConclusionOur NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

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“…Calcium-binding proteins play a vital role in the regulation of calcium homeostasis and signalling through diverse mechanisms, including modulation of intracellular calcium levels and transduction of intracellular [Ca 2+ ] signals [25,26]. CaBPs can also regulate energy metabolism, enzyme activity, cell proliferation and differentiation [27][28][29]. In particular, the deregulated expression of calmodulin, S100A8, S100A14, calbindin-D28k (CaBP28k) has been associated with cell survival and apoptotic pathways in several cancer models [30][31][32][33].…”

Section: Atp-mediated Protection Of Hk-2 Against Elevated Extracellul...mentioning

confidence: 99%

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

Hodeify

Ghani

Matar

et al. 2022

Cell Physiol Biochem

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Background/Aims: In kidney, extracellular [Ca2+] can modulate intracellular [Ca2+] to control key cellular processes. Hence, extracellular [Ca2+] is normally maintained within narrow range. We tested effect of extracellular ATP on viability of human proximal (HK-2) cells at high calcium. Modulation of intracellular calcium was assessed by imaging cytosolic [Ca2+], and expression of calcium-binding proteins (CaBPs). We present an artificial intelligence enabled deep learning model for prediction of injury and protection against extracellular [Ca2+] in HK-2 cells. Methods: HK-2 cells were cultured in calcium-free DMEM supplemented with CaCl2. Morphological changes were detected using light microscopy. Cell viability was determined using MTT Assay. Intracellular [Ca2+] was detected using fluorescence microscopy. For easy detection of HK-2 cells injury, we performed light microscopy image classification based on Convolutional Neural Network. Expression of CaBPs, p21, and Mcl-1 was measured using real-time PCR. Results: We show decreased viability of HK-2 cells cultured in elevated calcium levels, which was prevented by adenosine triphosphate (ATP). Exposure of cells to elevated extracellular [Ca2+] correlated with increasing fluorescence of intracellular calcium indicator, which was attenuated in presence of ATP. Since features cannot be detected easily by human eyes, we propose a customized deep learning-based CNN model for classification of HK-2 cells injury by extracellular calcium with high accuracy of 98%. Our data demonstrated significant increase in mRNA levels of calmodulin, S100A8, S100A14 and CaBP28k, with elevated extracellular [Ca2+]. Expression of these genes was enhanced with ATP. Conclusion: The results suggest that ATP protects human proximal (HK-2) cells against elevated extracellular calcium levels. We present a CNN model as user friendly tool to study calcium dependent injury in (HK-2) cells. Finally, we show that ATP-mediated protection is correlated with enhanced expression of calcium-binding proteins.

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Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells

Cited by 8 publications

References 37 publications

Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin

Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin

Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

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