1. Academic Validation
  2. CCR9 initiates epithelial-mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis

CCR9 initiates epithelial-mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis

  • Cancer Cell Int. 2021 Dec 4;21(1):648. doi: 10.1186/s12935-021-02320-0.
Haoran Kong  # 1 Wenhui Yu  # 2 Zhuning Chen  # 1 2 Haonan Li 2 Guiwen Ye 2 Jiacong Hong 2 Zhongyu Xie 2 Keng Chen 3 Yanfeng Wu 4 Huiyong Shen 5 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
  • 2 Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, Guangdong, 518033, People's Republic of China.
  • 3 Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, Guangdong, 518033, People's Republic of China. 47948842@qq.com.
  • 4 Center for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, Guangdong, 518033, People's Republic of China. wuyf@mail.sysu.edu.cn.
  • 5 Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China. shenhuiy@mail.sysu.edu.cn.
  • 6 Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, Guangdong, 518033, People's Republic of China. shenhuiy@mail.sysu.edu.cn.
  • # Contributed equally.
Abstract

Background: Osteosarcoma (OS) patients with lung metastasis have poor prognoses, and effective therapeutic strategies for delaying or inhibiting the spread of lung metastasis from the primary OS site are lacking. Hence, it is critical to elucidate the underlying mechanisms of OS metastasis and to identify additional new effective treatment strategies for patients.

Methods: Differential expression and functional analyses were performed to identify key genes and relevant signaling pathways associated with OS lung metastasis. The expression of CCR9 in OS cell lines and tissues was measured by RT-qPCR, western blotting and immunohistochemistry. Cell migration and invasion were assessed by wound healing and Transwell Matrigel invasion assays, respectively. The regulatory relationship between CCR9 and the Wnt/β-catenin signaling pathway was further evaluated by rescue experiments.

Results: The expression of CCR9 was elevated in OS cell lines and patients with lung metastasis. CCR9 promoted MG63 and HOS cell migration and invasion by activating the Wnt/β-catenin signaling pathway. Furthermore, knockdown of CCR9 repressed epithelial-mesenchymal transition (EMT) by downregulating mesenchymal markers (N-Cadherin and Vimentin) and EMT-associated transcription factors (twist and snail) and upregulating an epithelial marker (E-cadherin).

Conclusions: Our findings suggest that CCR9 promotes EMT by activating Wnt/β-catenin pathways to promote OS metastasis. CCR9 may be a promising therapeutic target to inhibit lung metastasis and serve as a novel prognostic marker for OS.

Keywords

CCR9; Epithelial–mesenchymal transition; Lung metastasis; Osteosarcoma; Wnt/β-catenin.

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