Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis

Experimental Cell Research
Pengfei LiJulie Chao

Abstract

Kallistatin is an endogenous protein that regulates differential signaling pathways and biological functions. Our previous studies showed that kallistatin gene therapy inhibited angiogenesis, tumor growth and metastasis in mice, and kallistatin protein suppressed Wnt-mediated growth, migration and invasion by blocking Wnt/β-catenin signaling pathway in breast cancer cells. In this study, we show that kallistatin reduced cell viability, and increased apoptotic cell death and caspase-3 activity in MDA-MB-231 breast cancer cells. Kallistatin also induced cancer cell autophagy, as evidenced by increased LC3B levels and elevated Atg5 and Beclin-1 expression; however, co-administration of Wnt or PPARγ antagonist GW9662 abolished these effects. Moreover, kallistatin via its heparin-binding site antagonized Wnt3a-induced cancer cell proliferation and increased PPARγ expression. Kallistatin inhibited oncogenic miR-21 synthesis associated with reduced Akt phosphorylation and Bcl-2 synthesis, but increased BAX expression. Kallistatin via PKC-ERK activation reduced miR-203 levels, leading to increased expression of suppressor of cytokine signaling 3 (SOCS3), a tumor suppressor. Conversely, kallistatin stimulated expression of the tumorigen...Continue Reading

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Citations

Feb 23, 2018·International Journal of Molecular Sciences·Elżbieta PawłowskaJanusz Blasiak
Jul 26, 2017·Biological Chemistry·Julie ChaoLee Chao
Jul 20, 2016·Hypertension·Julie ChaoLee Chao
Apr 27, 2019·Journal of Cellular Physiology·Alireza BahiraeeJafar Amani
Jun 18, 2019·Journal of Cellular Physiology·Shuyi ChenXiuling Zhi
Jan 22, 2020·Journal of Cellular Biochemistry·Meijuan LiuZhaozhong Cheng
May 13, 2020·Acta Biochimica Et Biophysica Sinica·Gang WangChaoke Tang
Jul 27, 2017·Oxidative Medicine and Cellular Longevity·Julie ChaoLee Chao
Oct 28, 2019·Antioxidants & Redox Signaling·Prem Prakash KushwahaShashank Kumar
Oct 9, 2019·International Journal of Molecular Sciences·Hui-Yi LohMohd Azuraidi Osman
Dec 6, 2019·Frontiers in Neurology·Yao JingHengli Tian
Feb 14, 2017·Histochemistry and Cell Biology·C M López FontanaR W Carón
Jan 2, 2021·Critical Reviews in Oncology/hematology·Shokooh SalimimoghadamBehzad Baradaran
Dec 31, 2020·International Journal of Molecular Sciences·Adele Vivacqua
Feb 18, 2021·Biomedical Engineering Online·Leonardo J Galvão-LimaElio J S S Barreto
Jun 29, 2021·Biochemical Genetics·Pirouz PourmohammadMohammad Nouri

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