Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells

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Asghar , M Y , Lassila , T , Paatero , I , Nguyen , V D , Kronqvist , P , Zhang , J , Slita , A , Lof , C , Zhou , Y , Rosenholm , J & Tornquist , K 2021 , ' Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells ' , Cellular and Molecular Life Sciences , vol. 78 , no. 15 , pp. 5827-5846 . https://doi.org/10.1007/s00018-021-03880-0

Title: Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells
Author: Asghar, Muhammad Yasir; Lassila, Taru; Paatero, Ilkka; Nguyen, Van Dien; Kronqvist, Pauliina; Zhang, Jixi; Slita, Anna; Lof, Christoffer; Zhou, You; Rosenholm, Jessica; Tornquist, Kid
Contributor: University of Helsinki, Medicum
Date: 2021-08
Language: eng
Number of pages: 20
Belongs to series: Cellular and Molecular Life Sciences
ISSN: 1420-682X
URI: http://hdl.handle.net/10138/333417
Abstract: Stromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remain elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared to primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced invasion, and the expression of promigratory sphingosine 1-phosphate and vascular endothelial growth factor-2 receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared to normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor, thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated invasion and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.
Subject: Thyroid cancer
Stromal interaction molecule 1 (STIM1)
ORAI1 calcium channel
Store-operated calcium entry (SOCE)
Migration
Invasion
Proliferation
SPHINGOSINE 1-PHOSPHATE
MIGRATION
CHANNELS
CALCIUM
HALLMARKS
ORAI1
METASTASIS
ZEBRAFISH
PATHWAYS
DELIVERY
1182 Biochemistry, cell and molecular biology
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