2. Academic Validation
  3. Formin-related protein 1 facilitates proliferation and aggressive phenotype of clear cell renal cell carcinoma through MAPK/MMP2 pathway

Formin-related protein 1 facilitates proliferation and aggressive phenotype of clear cell renal cell carcinoma through MAPK/MMP2 pathway

  • Mol Cell Probes. 2023 Jul 19;71:101921. doi: 10.1016/j.mcp.2023.101921.
Gui Ma 1,  Bin Zhang 2,  Shengjun Fu 2,  Jianzhong Lu 2,  Lili Zhang 2,  Panfeng Shang 3,  Zhongjin Yue 4
Affiliations

Affiliations

  • 1 Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China; Department of Pathology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310000, Zhejiang, China.
  • 2 Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
  • 3 Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. Electronic address: shangpf@lzu.edu.cn.
  • 4 Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. Electronic address: yuezhongjin@yeah.net.
PMID: 37454877 DOI: 10.1016/j.mcp.2023.101921
Abstract

Background: Formin-related protein-1(FRL1) has reportedly been overexpressed in a variety of malignancies, such as clear cell renal cell carcinoma (ccRCC). However, the clinical value and molecular mechanisms underlying ccRCC tumorigenesis and progression in association with FRL1 remain poorly understood.

Methods: Immunohistochemical analysis was performed on 119 paraffin-embedded RCC tissue samples to detect FRL1 expression and analyze its prognostic value. Colony formation, the CCK-8 assay, flow cytometry, and in vivo nude mice subcutaneous experiments were used to identify the effects of FRL1 on growth and proliferation. In vitro tests for wound healing, migration, and invasion were used to assess the involvement of FRL1 in invasion and metastatic potential. The process of epithelial-mesenchymal transition process (EMT) and the MMP2 expression were detected in stably transfected RCC cells via western blotting, as well as in tumor tissue paraffin sections from xenograft model.

Results: Both FRL1 mRNA and protein levels were noticeably elevated in ccRCC cell lines and samples. Aberrant overexpression of FRL1 was associated with unfavorable clinicopathological features of ccRCC and indicated poor prognosis. Ectopic overexpression of FRL1 increased the growth-promoting traits of ccRCC cells as well as the migratory and invasive capacity of RCC cells, whereas FRL1-silencing caused the opposite results. In addition, FRL1 promoted epithelial-mesenchymal transition (EMT) and upregulated the expression of matrix metalloproteinase 2 (MMP2). Finally, overexpression of FRL1 upregulated phosphorylation level of ERK1/2 with no effect on total level of ERK1/2 in the RCC cells. MAPK/ERK Inhibitor reversed the promotional effects of FRL1.

Conclusion: FRL1 was overexpressed in ccRCC tissues and predicted poor prognosis. FRL1 contributes to invasion and aggressive phenotype of ccRCC by facilitating EMT through MAPK/MMP2 axis.

Keywords

EMT; FRL1; MAPK/MMP2 pathway; ccRCC.

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