Research Paper Volume 12, Issue 13 pp 13059—13075
Loss of AKR1B10 promotes colorectal cancer cells proliferation and migration via regulating FGF1-dependent pathway
- 1 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- 2 Suzhou Emergency Center, Suzhou, Jiangsu, China
Received: December 24, 2019 Accepted: May 1, 2020 Published: July 2, 2020https://doi.org/10.18632/aging.103393
How to Cite
Copyright © 2020 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Colorectal cancer (CRC) is a common malignancy worldwide with poor prognosis and survival rates. The aldo-keto reductase family 1 member B10 (AKR1B10) plays an important role in metabolism, cell proliferation and mobility, and is downregulated in CRC. We hypothesized that AKR1B10 would promote CRC genesis via a noncanonical oncogenic pathway and is a novel therapeutic target. In this study, AKR1B10 expression levels in 135 pairs of CRC and para-tumor tissues were examined, and its oncogenic role was determined using in vitro and in vivo functional assays following genetic manipulation of CRC cells. AKR1B10 was downregulated in CRC tissues compared to the adjacent normal colorectal tissues, and associated with the clinicopathological status of the patients. AKR1B10 depletion promoted the proliferation and migration of CRC cells in vitro, while its ectopic expression had the opposite effect. AKR1B10 was also significantly correlated with FGF1 gene and protein levels. Knockdown of AKR1B10 promoted tumor growth in vivo, and increased the expression of FGF1. Finally, AKR1B10 inhibited FGF1, and suppressed the proliferation and migration ability of CRC cells in an FGF1-dependent manner. In conclusion, AKR1B10 acts as a tumor suppressor in CRC by inactivating FGF1, and is a novel target for combination therapy of CRC.