Regulation and Role of Store-Operated Ca2+ Entry in Cellular Proliferation

Hodeify, Rawad; Yu, Fang; Courjaret, Raphael Jean; Nader, Nancy; Dib, Maya; Sun, Lu; Adap, Ethel; Hubrack, Satanay; Machaca, Khaled

doi:10.1201/9781315152592-12

Cited by 28 publications

(30 citation statements)

References 137 publications

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“…SOCE, a main pathway of extracellular Ca [2]+ influx, plays a significant role in extracellular Ca [2]+ homeostasis in almost all cellular pathways [32]. SOCE is important for the regulation of contraction, cell proliferation and apoptosis, which are pathways implicated in cancer pathogenesis [33,34]. In the present study, we inhibited STIM1, the key component of SOCE, which attenuated Ca [2]+ influx and suppressed A549 and SK-MES-1 cell proliferation.…”

Section: Discussionmentioning

confidence: 61%

Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts

Zeng

et al. 2019

Bioengineered

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Stromal interaction molecule 1 (STIM1) is a calcium-sensing protein localized in the membrane of the endoplasmic reticulum. The expression of STIM1 has been shown to be closely associated with cell proliferation. The aim of the present study was to investigate the role of STIM1 in the regulation of cancer progression and its clinical relevance. The data demonstrated that the expression of the STIM1 was significantly higher in non-small-cell lung cancer (NSCLC) tissues than in benign lesions and was associated with advanced NSCLC T stage. Knockdown of STIM1 expression in NSCLC cell lines A549 and SK-MES-1 significantly inhibited cell proliferation and induces A549 and SK-MES-1 cell arrest at the G2/M and S phases of the cell cycle. Western blotting showed that the expression of cyclin-dependent kinase (CDK) 1 and CDK2 were reduced while knockdown of STIM1 expression. Furthermore, knockdown of STIM1 in NSCLC cells significantly reduced the levels of xenograft tumor growth in nude mice. These data indicate that aberrant expression of the STIM1 protein may contribute to NSCLC progression. Future studies should focus on targeting STIM1 as a novel strategy for NSCLC therapy.

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Section: Discussionmentioning

confidence: 61%

Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts

Zeng

et al. 2019

Bioengineered

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“…The membrane potential of living cancer stem cells in hepatocellular carcinoma has a lower negative charge than that of normal stem cells [16]. Thus, it has been confirmed that the membrane potential of living cells involves various cellular biological activities [17][18][19][20]. However, fixed cells lose the dynamics of the membrane potential, since the intracellular metabolism with ion dynamics ceases to exist.…”

Section: Discussionmentioning

confidence: 95%

Measurement and visualization of cell membrane surface charge in fixed cultured cells related with cell morphology

et al. 2020

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The diagnosis of patients with malignancies relies on the results of a clinical cytological examination. To enhance the diagnostic qualities of cytological examinations, it is important to have a detailed analysis of the cell's characteristics. There is, therefore, a need for developing a new auxiliary method for cytological diagnosis. In this study, we focused on studying the charge of the cell membrane surface of fixed cells, which is one of important cell's characteristics. Although fixed cells lose membrane potential which is observed in living cells owing to ion dynamics, we hypothesized that fixed cells still have a cell membrane surface charge due to cell membrane components and structure. We used 5 cell lines in this study (ARO, C32TG, RT4, TK, UM-UC-14). After fixation with CytoRich Red, we measured the cell membrane surface charge of fixed cells in solution using zeta potential measurements and fixed cells on glass slides, visualizing it using antibody-labeled beads and positivelycharged beads. Furthermore, we measured the cell membrane surface charge of fixed cells under different conditions, such as different solution of fixative, ion concentration, pH, and pepsin treatments. The zeta potential measurements and visualization using the beads indicated that the cell membrane surface of fixed cells was negatively charged, and also that the charge varied among fixed cells. The charge state was affected by the different treatments. Moreover, the number of cell-bound beads was small in interphase, anaphase, and apoptotic cells. We concluded that the negative cell membrane surface charge was influenced by the three-dimensional structure of proteins as well as the different types of amino acids and lipids on the cell membrane. Thus, cell surface charge visualization can be applied as a new auxiliary method for clinical cytological diagnosis. This is the first systematic report of the cell membrane surface charge of fixed cells.

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“…This was concluded based on the observation that downregulating Orai or STIM by shRNAs or CaMK-II inhibition suppressed the CaMK-II/MAPK signaling pathway, resulting in the inhibition of human melanoma cells migration and metastasis in the lungs [217]. For a detailed review on the role of the Orai/STIM system in tumor cells invasiveness and the development of metastasis, see [218], and for a review on the role of CaMK-II in cellular scattering, and actin cytoskeleton dynamics leading to the rupture of cell-cell adhesion as a key feature of EMT, see [132].…”

Section: Cam-dependent Protein Kinasesmentioning

confidence: 99%

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

Villalobo

Berchtold

2020

IJMS

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Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.

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Regulation and Role of Store-Operated Ca2+ Entry in Cellular Proliferation

Cited by 28 publications

References 137 publications

Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts

Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts

Measurement and visualization of cell membrane surface charge in fixed cultured cells related with cell morphology

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

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