RanBP1: 肺癌和胶质瘤癌干细胞的潜在治疗靶点。
RanBP1: A Potential Therapeutic Target for Cancer Stem Cells in Lung Cancer and Glioma.
发表日期:2023 Apr 06
作者:
Yeon-Jee Kahm, In-Gyu Kim, Rae-Kwon Kim
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
癌症干细胞(CSCs)是使癌症治疗困难的因素之一。因此,许多研究人员正在开展研究以有效摧毁CSCs。因此,我们试图提出一种能够有效抑制CSCs的新靶点。在本研究中,我们观察到肺癌干细胞(LCSCs)和胶质瘤干细胞(GSCs)中Ran结合蛋白1(RanBP1)的高表达。上调的RanBP1表达与CSC标记蛋白和CSC调节因子的表达强烈相关。此外,升高的RanBP1表达与病人预后不良密切相关。CSCs具有抵抗辐射的能力,而RanBP1调节这种能力。RanBP1还影响与转移相关的上皮间质转化(EMT)现象。EMT标记蛋白和调节蛋白受RanBP1表达的影响,细胞活动性也随RanBP1表达而调节。癌症微环境影响癌症的生长、转移和治疗。RanBP1通过调节细胞因子IL-18来调节癌症微环境。分泌的IL-18作用于癌细胞并促进癌恶性。我们的研究首次揭示RanBP1在LCSCs和GSCs中是一个重要的调节因子,提示其具有潜在的治疗靶点。
Cancer stem cells (CSCs) are known to be one of the factors that make cancer treatment difficult. Many researchers are thus conducting research to efficiently destroy CSCs. Therefore, we sought to suggest a new target that can efficiently suppress CSCs. In this study, we observed a high expression of Ran-binding protein 1 (RanBP1) in lung cancer stem cells (LCSCs) and glioma stem cells (GSCs). Upregulated RanBP1 expression is strongly associated with the expression of CSC marker proteins and CSC regulators. In addition, an elevated RanBP1 expression is strongly associated with a poor patient prognosis. CSCs have the ability to resist radiation, and RanBP1 regulates this ability. RanBP1 also affects the metastasis-associated epithelial-mesenchymal transition (EMT) phenomenon. EMT marker proteins and regulatory proteins are affected by RanBP1 expression, and cell motility was regulated according to RanBP1 expression. The cancer microenvironment influences cancer growth, metastasis, and cancer treatment. RanBP1 can modulate the cancer microenvironment by regulating the cytokine IL-18. Secreted IL-18 acts on cancer cells and promotes cancer malignancy. Our results reveal, for the first time, that RanBP1 is an important regulator in LCSCs and GSCs, suggesting that it holds potential for use as a potential therapeutic target.