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

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.