Samriddhi Arora,1 Jyoti Tanwar,2,3 Nutan Sharma,1 Suman Saurav,1 and Rajender K. Motiani1,*
"1Laboratory of Calciomics and Systemic Pathophysiology (LCSP), Regional Centre for Biotechnology (RCB), Faridabad 121001, India; [email protected] (S.A.); [email protected] (N.S.); [email protected] (S.S.)
2CSIR-Institute of Genomics and Integrative Biology (IGIB), New Delhi 110025, India; [email protected]
3Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
*Correspondence: [email protected]"
Calcium Imaging, Medical Research
"Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous Ca2+ influx pathway. Although the role of Orai1 channels is well studied, the significance of Orai2/3 channels is still emerging in nature. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in six PC cell lines and found that Orai3 forms a functional SOCE channel in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first-time reports that Orai3 drives aggressive phenotypes of PC cells, i.e., migration in vitro and metastasis in vivo. Considering that Orai3 overexpression leads to poor prognosis in PC patients, it appears to be a highly attractive therapeutic target.
Keywords: Orai3, store operated calcium entry, pancreatic cancer, metastasis
DOI: https://dx.doi.org/ 10.3390/cancers13235937
A digital fluorescence imaging system (Nikon Eclipse Ti2 microscope coupled with CoolLED pE-340 Fura light source
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The 340 nm and 380 nm LED illumination system provides the optimum excitation wavelengths for Fura-2-based calcium imaging, allowing high-precision, stable, high-throughput imaging with video-rate time resolution.
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