Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells
Küçük Resim Yok
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bmc
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
BackgroundThe endoplasmic reticulum (ER) Ca2+ sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca2+ entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study investigated the functional consequences of enhanced expression of STIM1 and Orai1 in a tumor-initiating subpopulation of Huh-7hepatocellular carcinoma (HCC) cells that express epithelial cell adhesion molecule (EpCAM) and Prominin 1 (CD133).MethodsWe performed qRT-PCR, intracellular Ca2+ monitoring, protein analyses, and real-time cell proliferation assays on EpCAM(+)CD133(+) subpopulation of tumor-initiating Huh-7 HCC cells expressing high levels of STIM1 and/or Orai1. Statistical significance between the means of two groups was evaluated using unpaired Student's t-test.ResultsEnhanced STIM1 expression significantly increased ER Ca2+ release and proliferation rate of EpCAM(+)CD133(+) cells.ConclusionSTIM1 overexpression may facilitate cancer cell survival by increasing ER Ca2+-buffering capacity, which makes more Ca2+ available for the cytosolic events, on the other hand, possibly preventing Ca2+-dependent enzymatic activity in mitochondria whose Ca2+ uniporter requires much higher cytosolic Ca2+ levels.
Açıklama
Anahtar Kelimeler
HCC, SOCE, TIC, STIM1, Orai1, Ca2+
Kaynak
Bmc Cancer
WoS Q Değeri
Q3
Scopus Q Değeri
Q1
Cilt
19
