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人骨肉瘤细胞中hSlo钾通道的沉默促进肿瘤发生。

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis.

作者信息

Cambien Béatrice, Rezzonico Roger, Vitale Sébastien, Rouzaire-Dubois Béatrice, Dubois Jean-Marc, Barthel Robert, Soilihi Babou Karimdjee, Mograbi Baharia, Schmid-Alliana Annie, Schmid-Antomarchi Heidy

机构信息

Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.

INSERM, U638, Nice F-06107, France.

出版信息

Int J Cancer. 2008 Jul 15;123(2):365-371. doi: 10.1002/ijc.23511.

Abstract

Potassium channels, the most diverse superfamily of ion channels, have recently emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large conductance Ca(2+)-activated K(+) channels, often referred to as BK channels, are at the crossroads of several tumor-associated processes such as cell proliferation, survival, secretion and migration. Despite the high BK channel expression in osteosarcoma (OS), their function has not yet been investigated in this malignant bone pathology. Here, using stable RNA interference to reduce the expression of hSlo, the human pore-forming alpha-subunit of the BK channel, in human Cal72 OS cells, we show that BK channels play a functional role in carcinogenesis. Our results reveal for the first time that BK channels exhibit antitumoral properties in OS in vivo and affect the tumor microenvironment through the modulation of both chemokine expression and leukocyte infiltration.

摘要

钾通道是离子通道中最多样化的超家族,最近已成为癌症发生的调节因子,从而为抗癌斗争引入了可能的新治疗策略。特别是,大电导钙激活钾通道,通常称为BK通道,处于几个与肿瘤相关的过程的交叉点,如细胞增殖、存活、分泌和迁移。尽管BK通道在骨肉瘤(OS)中高表达,但其在这种恶性骨病理中的功能尚未得到研究。在这里,我们使用稳定的RNA干扰来降低人Cal72 OS细胞中BK通道的人孔形成α亚基hSlo的表达,结果表明BK通道在癌症发生中发挥功能作用。我们的结果首次揭示,BK通道在体内骨肉瘤中具有抗肿瘤特性,并通过调节趋化因子表达和白细胞浸润来影响肿瘤微环境。

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