ReviewThe dose-dependent effect of SOX9 and its incidence in colorectal cancer

- SOX9 has a dose-dependent effect in intestine epithelial cells.
- High dose of SOX9 is found in quiescent reserve intestinal stem cells.
- Low dose of SOX9 is found in actively proliferating intestinal stem cells.
- High level of SOX9 predicts a low risk of relapse in stage II CRC.
- 10% of colorectal cancers exhibit heterozygous inactivating mutations of SOX9.

A member of the Sry-related HMG-box family of transcription factors (SOX9) is a transcription factor that belongs to the superfamily of High Mobility Group (HMG) domain transcription factors. SOX9 is expressed in a variety of tissues, including as the intestinal epithelium, where it is now recognised as an important actor for homeostasis. Beside, a high level of SOX9 has recently been correlated with a good prognosis for stage II colorectal cancers. However, growing evidence indicates that deciphering the function of SOX9 in the intestine has to take into account a dose-dependent effect of SOX9. Given the recurrent controversies and the lack of a state of the art as to whether SOX9 behaves like a tumour suppressor or an oncogen in the intestine epithelium, it is time to provide an update of the accumulated knowledge about the biological function of SOX9 in the intestine and about the role of SOX9 in colorectal cancers.