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. 2022 Nov 29;114(3):822–836. doi: 10.1111/cas.15652

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© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Increased levels of Rac1 activate the PI3K/AKT signaling pathway, thereby increasing SOX9 expression in colon cancer cells. Increased SOX9 expression activates the hexokinase (HK2) and glucose‐6‐phosphate dehydrogenase (G6PD) promoter and promotes the expression of HK2 and G6PD at the transcriptional level, then enhances glycolysis and the pentose phosphate pathway to enhance proliferation, invasion, and migration. We further revealed novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.