Yuwei Ling1, Qi Cao2, Yihan Liu2, Jing Zhao1, Ye Zhao1, Kaifu Li1, Zhiqiang Chen1, Xiaoyan Du2, Xueyun Huo3, Hua Kang4, Zhenwen Chen2. 1. Department of General Surgery, Center for Thyroid and Breast Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. 2. School of Basic Medical Sciences, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, 100069, China. 3. School of Basic Medical Sciences, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, 100069, China. huoxueyun@ccmu.edu.cn. 4. Department of General Surgery, Center for Thyroid and Breast Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. kanghua@xwh.ccmu.edu.cn.
Abstract
BACKGROUND: Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC. METHODS: PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-β/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice. RESULTS: PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial‑to‑mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo. CONCLUSIONS: Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.
BACKGROUND: Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC. METHODS:PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-β/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice. RESULTS:PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial‑to‑mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo. CONCLUSIONS: Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancerpatients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.
Entities:
Keywords:
Epithelial-to-mesenchymal transition; PFN2; Triple negative breast cancer
Authors: Tao Wang; Liqun Dai; Shu Shen; Yi Yang; Ming Yang; Xianwei Yang; Yiwen Qiu; Wentao Wang Journal: Front Immunol Date: 2022-05-27 Impact factor: 8.786