1. Academic Validation
  2. SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

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

  • Front Cell Dev Biol. 2021 Jun 25;9:678967. doi: 10.3389/fcell.2021.678967.
Zhao-Ming Xiao 1 Dao-Jun Lv 2 Yu-Zhong Yu 1 Chong Wang 1 Tao Xie 1 Tao Wang 1 Xian-Lu Song 3 Shan-Chao Zhao 1 4
Affiliations

Affiliations

  • 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Guangdong Key Laboratory of Urology, Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
  • 4 Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Abstract

Background: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) 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 SMARCC1 in PCa and explore the underlying regulatory mechanisms.

Methods: The expression of SMARCC1 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 SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.

Results: Our finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/Akt pathway in PCa cells.

Conclusion: SMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/Akt signaling pathway and is a novel therapeutic target.

Keywords

PI3K/AKT pathway; SMARCC1; epithelial-mesenchymal-transition; proliferation; prostate cancer.

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