AUTHOR=Xiao Zhao-Ming , Lv Dao-Jun , Yu Yu-zhong , Wang Chong , Xie Tao , Wang Tao , Song Xian-Lu , Zhao Shan-Chao 

TITLE=SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.678967

DOI=10.3389/fcell.2021.678967

ISSN=2296-634X

ABSTRACT=<sec><title>Background</title><p>SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (<italic>SMARCC1</italic>) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of <italic>SMARCC1</italic> in PCa and explore the underlying regulatory mechanisms.</p></sec><sec><title>Methods</title><p>The expression of <italic>SMARCC1</italic> was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with <italic>SMARCC1</italic> depletion both <italic>in vitro</italic> and <italic>in vivo</italic>. The expression levels of relevant proteins were detected by Western blotting.</p></sec><sec><title>Results</title><p>Our finding showed that <italic>SMARCC1</italic> was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of <italic>SMARCC1</italic> was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of <italic>SMARCC1</italic> dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of <italic>SMARCC1</italic> facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of <italic>SMARCC1</italic> activated the <italic>PI3K/AKT</italic> pathway in PCa cells.</p></sec><sec><title>Conclusion</title><p><italic>SMARCC1</italic> suppresses PCa cell proliferation and metastasis <italic>via</italic> the <italic>PI3K/AKT</italic> signaling pathway and is a novel therapeutic target.</p></sec>