GFPT2 promotes metastasis and forms a positive feedback loop with p65 in colorectal cancer

Colorectal Cancer
10/09/2020

Am J Cancer Res. 2020 Aug 1;10(8):2510-2522. eCollection 2020.

ABSTRACT

As a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which is responsible for glycosylation, Glutamine fructose-6-phosphate amidotransferase 2 (GFPT2) is involved in human breast and lung tumorigenesis. However, whether GFTP2 is associated with tumor metastasis remains unclear. Here, we found that GFPT2 promoted the proliferation, migration, invasion and metastasis of colorectal cancer (CRC) cells. Mechanically, p65 acted as an upstream transcription factor of GFPT2 and


regulated its expression and function. In turn, GFPT2 enhanced the glycosylation of p65, which led to the nuclear translocation of p65 and then activated NF-κB pathway. Thus, GFTP2 and p65 formed a positive feedback loop to promote the progression of CRC. In addition, GFPT2 was up-regulated in CRC tissues and closely related with liver metastasis (P<0.0001) and tumor stage (P=0.0184). High expression of GFPT2 predicted poor prognosis for CRC patients. Moreover, GFTP2 expression was positively linked with O-linked N-acetylglucosamine transferase in CRC tissues. Our study reveals a new mechanism of GFPT2 in CRC metastasis and provides a new target therapeutic target to deter metastasis.