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SIX3 function in cancer: progression and comprehensive analysis

Abstract

The homeobox gene family encodes transcription factors that are essential for cell growth, proliferation, and differentiation, and its dysfunction is linked to tumor initiation and progression. Sine oculis homeobox (SIX) belongs to the homeobox gene family, with SIX3 being a core member. Recent studies indicate that SXI3 functions as a cancer suppressor or promoter, which is mainly dependent on SIX3’s influence on the signal pathways that promote or inhibit cancer in cells. The low expression of SIX3 in most malignant tumors was confirmed by detailed studies, which could promote the cell cycle, proliferation, migration, and angiogenesis. The recovery or upregulation of SIX3 expression to suppress cancer is closely related to the direct or indirect inhibition of the Wnt pathway. However, in some malignancies, such as esophageal cancer and gastric cancer, SIX3 is a tumor-promoting factor, and repressing SIX3 improves patients’ prognosis. This review introduces the research progress of SIX3 in tumors and gives a comprehensive analysis, intending to explain why SIX3 plays different roles in different cancers and provide new cancer therapy strategies.

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Fig. 1: SIX3-related signal network.
Fig. 2: Regulation mechanism of SIX3 expression and its tumor-suppressing role in cancer.

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Acknowledgements

We thank Yi-he Hu and Jie Xie for the critical reading of the manuscript. Figure 2 was created by Figdraw (WWW.Figdraw.com), for which we are grateful. We apologize to those authors whose primary work we did not directly reference due to space restrictions.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81974339) and the Science and Technology Plan Project of Hunan Province (Grant No. 2019JJ40499).

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T-LM and PZ wrote the original draft. T-LM, PZ and J-XC participated in writing and editing the review. PZ and J-XC prepared the figures. Y-HH and JX edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yi-He Hu or Jie Xie.

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Ma, TL., Zhu, P., Chen, JX. et al. SIX3 function in cancer: progression and comprehensive analysis. Cancer Gene Ther 29, 1542–1549 (2022). https://doi.org/10.1038/s41417-022-00488-9

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