Background/purpose: Return of Ca to endoplasmic reticulum is mediated by Orai/STIM-mediated store-operated Ca entry (SOCE) channel. We aimed to investigate Orai1 and STIM1 expressions in human oral carcinogenesis.
Materials And Methods: Sixty-six oral squamous cell carcinomas (OSCCs), 14 oral potentially malignant disorders (OPMD) with moderate-severe oral epithelial dysplasia (OED), 19 OPMD with mild OED, and 14 normal oral mucosa (NOM) samples were subjected to immunohistochemical staining. Two human oral cancer cell lines (OCCLs), an oral premalignant cell line (DOK), and a normal oral keratinocyte culture (HOK) were used for Western blot and real-time quantitative reverse transcription-polymerase chain reaction. OCCLs were evaluated for proliferation, migration, and invasion assays.
Results: Orai1 and STIM1 protein and mRNA expressions in OSCC were significantly enhanced as compared with normal samples. Protein expressions of Orai1 and STIM1 in OCCLs were significantly enhanced as compared with HOK. Significant decreases in degrees of proliferation, migration and invasion were noted in OCCLs with and siRNA transfection as compared with those without transfection. Significantly increased Orai1 and STIM1 protein levels were noted in OPMD with moderate-severe OED as compared with those with mild OED.
Conclusion: Our results indicate that Orai1 and STIM1 overexpression is associated with human oral carcinogenesis.
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http://dx.doi.org/10.1016/j.jds.2021.07.004 | DOI Listing |
Am J Physiol Cell Physiol
January 2025
Department of Physiology (Cellular Physiology Research Group),Institute of Molecular Pathology Biomarkers (IMPB), University of Extremadura, 10003-Caceres, Spain.
Filamin A (FLNA) is an actin-binding protein that has been reported to interact with STIM1 modulating the activation of Orai1 channels. Cleaving of FLNA by calpain leads to a C-terminal fragment that is involved in a variety of functional and pathological events, including pro-oncogenic activity in different types of cancer. Here we show that full-length FLNA is downregulated in samples from colon cancer patients as well as in the adenocarcinoma cell line HT-29.
View Article and Find Full Text PDFSci Transl Med
December 2024
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous.
View Article and Find Full Text PDFUnlabelled: Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicated in the development of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), a fatal and progressive lung vascular disease. Transforming growth factor β (TGF-β ), an inflammatory cytokine, is known to induce EndMT in many types of endothelial cells including lung vascular endothelial cells (LVEC).
View Article and Find Full Text PDFCell Calcium
January 2025
Cell Death Research and Therapy Laboratory, Center for Cancer Biology, VIB-KU Leuven, Leuven, Belgium; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. Electronic address:
The endoplasmic reticulum (ER) controls intracellular Ca dynamics. Depletion of ER Ca stores results in short-term activation of store-operated Ca entry (SOCE) via STIM1/Orai1 at ER-plasma membrane (ER-PM) contact sites (MCSs) and the long-term activation of the unfolded protein response (UPR), securing ER proteostasis. Recent work by Carreras-Sureda and colleagues describes a bidirectional control between IRE1 and STIM1 within the ER lumen that regulates ER-PM contact assembly and SOCE to sustain T-cell activation and myoblast differentiation.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas, United States.
Store-operated calcium (Ca) entry (SOCE) represents a major route of Ca permeation across the plasma membrane (PM) in nonexcitable cells, which plays an indispensable role in maintaining intracellular Ca homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to the translocation of activated STIM1 toward the PM.
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