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SOX4 promotes the growth and metastasis of breast cancer

Authors
  • Zhang, Jing1, 2
  • Xiao, Chunhua2, 3
  • Feng, Zhenbo2, 4
  • Gong, Yun2
  • Sun, Baohua2
  • Li, Zhongqi1
  • Lu, Yimin1
  • Fei, Xiaojie1
  • Wu, Weizhu5
  • Sun, Xiaoping2
  • Teng, Lisong1
  • 1 The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China , Hangzhou (China)
  • 2 The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA , Houston (United States)
  • 3 National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People’s Republic of China , Tianjin (China)
  • 4 The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China , Nanning (China)
  • 5 Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China , Ningbo (China)
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 29, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12935-020-01568-2
Source
Springer Nature
Keywords
License
Green

Abstract

PurposeIncreasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo.MethodsWe used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging.ResultsSOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel.ConclusionsSOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

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