High aldehyde dehydrogenase 3B2 (ALDH3B2) expression in cholangiocarcinoma promotes tumor metastasis, a new study published in the journal Cell Death and Disease found.

It does so by upregulating integrin β1 (ITGB1) and the phosphorylation levels of c-Jun, p38, and ERK. Patients with high expression of ALDH3B2 also have high expression of ITGB1 in intrahepatic, perihilar, and distant cholangiocarcinoma, the authors said.

“ALDH3B2 can be regarded as a potential poor prognostic marker for cholangiocarcinoma and that ALDH3B2 may serve as a promising treatment target,” they wrote.


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It was already known that aldehyde dehydrogenase played an important role in regulating tumor progression. However, their role in cholangiocarcinoma had not been clarified. In the present study, a team of researchers from China analyzed the expression of aldehyde dehydrogenases in 8 paired tumor and peritumor perihilar cholangiocarcinoma tissues.

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They found that 2 aldehyde dehydrogenases, ALDH3B1 and ALDH3B2, were upregulated in tumor tissues. They also found that ALDH3B2 was an independent prognostic factor in both perihilar and intrahepatic cholangiocarcinoma.

The expression of ALDH3B2 was also associated with serum carcinoembryonic antigen in intrahepatic and distant cholangiocarcinoma and associated with tumor T stage, M stage, neural invasion, and serum CA19-9 in perihilar cholangiocarcinoma.

The researchers also conducted cell culture experiments and found that ALDH3B2 overexpression drove cell proliferation and clone formation. On the contrary, knocking down ALDH3B2 inhibited cell migration, invasion, and epithelial to mesenchymal transition.

Knocking down ALDH3B2 also downregulated ITGB1 expression and inhibited c-Jun, p38, and ERK phosphorylation. It inhibited the effect of ALDH3B2 overexpression on cell proliferation, migration, and invasion. In experiments conducted on mice, ALDH3B2 knockdown restrained tumor metastasis.

“The double-positive expression of ITGB1 and ALDH3B2 serves as a better prognostic biomarker of [cholangiocarcinoma],” the authors concluded.

Reference

Wang Y, Li K, Zhao W, et al. Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression. Cell Death Dis. 2021;14(12):1158. doi:10.1038/s41419-021-04451-8