Aberrantly High Expression of Steroid Receptor Coactivator-1 Drives Lung Cancer Growth and Metastasis by Enhancing Cancer Stemness.

IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Jinjin Pan, Haoran Zhou, Liang Liu, Shuo Xu, Yu Hou, Ke Cheng, Yuan Li, Chenggong Zhu, Na Wu, Chunmei Bai, Ruoqing Wang, Changhong Liu, Rui Wang, Yuhui Yuan
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Abstract

Steroid receptor coactivator-1 (SRC-1) is documented in various cancers and primarily mediates tumor growth and metastasis. Nevertheless, the specific effects and underlying mechanisms of SRC-1 in lung cancer have not been fully explored. This study aims to elucidate the role of SRC-1 in lung cancer progression and its impact on cancer stemness. In this study, we found that SRC-1 was expressed higher in human lung cancer tissues compared to normal lung tissues, with a positive correlation between SRC-1 expression and rates of distant metastasis and lymph node involvement. High SRC-1 expression was correlated with a poor prognosis of lung cancer. In vitro, silencing SRC-1 in lung cancer cell lines repressed cell proliferation, invasion, migration, and enhanced the sensitivity of lung cancer cells to gefitinib. In vivo, silencing SRC-1 in lung cancer cells decreased tumor size and weight in a subcutaneous xenograft mouse model. Furthermore, SRC-1 knockdown inhibited the lung metastasis and reduced twist1 expression. Mechanistically, SRC-1 promoted sphere formation and induced increased expression of the markers of cancer stem cells in lung cancer cells. Besides, SRC-1 positively correlated with c-Myc in human lung cancer. Overexpression of SRC-1 in lung cancer cell lines up-regulated mRNA and protein expression of c-Myc, suggesting that SRC-1 may enhance lung cancer stemness via up-regulating c-Myc. This study demonstrated that aberrantly high levels of SRC-1 in lung cancer contribute to tumor growth and metastasis by enhancing cancer stemness, suggesting that targeting SRC-1 could be a novel potential therapeutic strategy in the treatment of lung cancer.

类固醇受体共激活因子-1的异常高表达通过增强肿瘤干性驱动肺癌生长和转移。
类固醇受体共激活因子-1 (SRC-1)在多种癌症中均有记载,主要介导肿瘤生长和转移。然而,SRC-1在肺癌中的具体作用和潜在机制尚未得到充分探讨。本研究旨在阐明SRC-1在肺癌进展中的作用及其对癌变的影响。在本研究中,我们发现SRC-1在人肺癌组织中的表达高于正常肺组织,并且SRC-1的表达与远处转移率和淋巴结受累率呈正相关。SRC-1高表达与肺癌预后不良相关。在体外实验中,在肺癌细胞系中沉默SRC-1可抑制细胞增殖、侵袭、迁移,增强肺癌细胞对吉非替尼的敏感性。在体内,在皮下异种移植小鼠模型中,沉默肺癌细胞中的SRC-1可减少肿瘤的大小和重量。此外,SRC-1敲低可抑制肺转移并降低twist1的表达。在机制上,SRC-1促进肺癌细胞球的形成,诱导肿瘤干细胞标志物的表达增加。此外,SRC-1在人肺癌中与c-Myc呈正相关。SRC-1在肺癌细胞系中过表达可上调c-Myc mRNA和蛋白的表达,提示SRC-1可能通过上调c-Myc而增强肺癌的干性。本研究表明,肺癌中异常高水平的SRC-1通过增强肿瘤的干性来促进肿瘤的生长和转移,提示靶向SRC-1可能是治疗肺癌的一种新的潜在治疗策略。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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