J Cancer 2021; 12(7):2050-2058. doi:10.7150/jca.51494

Research Paper

Syntaxin 2 promotes colorectal cancer growth by increasing the secretion of exosomes

Yongxia Wang1,2,3, Yongzhen Li1,2,3, Hong Zhou2, Xinlai Qian1,2,3✉, Yuhan Hu1,2,3✉

1. Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.
2. Department of Pathology, Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan, China.
3. Henan Provincial Key Laboratory of Molecular Tumor Pathology, Henan, Xinxiang, China.

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Citation:
Wang Y, Li Y, Zhou H, Qian X, Hu Y. Syntaxin 2 promotes colorectal cancer growth by increasing the secretion of exosomes. J Cancer 2021; 12(7):2050-2058. doi:10.7150/jca.51494. Available from https://www.jcancer.org/v12p2050.htm

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Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers with high mortality worldwide. Uncontrolled growth is an important hallmark of CRC. However, the mechanisms are poorly understood. Methods: Syntaxin 2 (STX2) expression was analyzed in 160 cases of paraffin-embedded CRC tissue by immunohistochemistry, in 10 cases of fresh CRC tissue by western blot, and in 2 public databases. Gain- and loss-of-function analyses were used to investigate the biological function of STX2 in CRC growth. Exosomes isolation, characterization, Co-immunoprecipitation (Co-IP), flow cytometry and fluorescence were conducted to study the molecular mechanism of STX2 in CRC growth. Results: The expression of STX2 was obviously up-regulated in human CRC tissues. Overexpression of STX2 increased the growth of CRC cells in vitro and in vivo. Downregulation of STX2 repressed the growth of CRC. STX2 modulated exosomes secretion of CRC cells which might correlated with Rab8a expression. The secreted exosomes could be ingested by CRC cells, and ultimately promoted the growth of CRC by arresting the tumor cells at S phase. Conclusions: Our data provide evidence that STX2 promotes CRC growth by increasing exosomes secretion of CRC cells; And the modulation of STX2 in exosomes secretion correlates with Rab8a. Thus, our study identified a new mechanism of STX2 in CRC growth and may provide a possible strategy for CRC therapy.

Keywords: Syntaxin 2, colorectal cancer, growth, exosomes.