The role of PFKFB3 in maintaining colorectal cancer cell proliferation and stemness

Since generally confronting with the hypoxic and stressful microenvironment, cancer cells alter their glucose metabolism pattern to glycolysis to sustain the continuous proliferation and vigorous biological activities. Bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) isoform 3 (PFKFB3) functions as an effectively modulator of glycolysis and also participates in regulating angiogenesis, cell death and cell stemness. Meanwhile, PFKFB3 is highly expressed in a variety of cancer cells, and can be activated by several regulatory factors, such as hypoxia, inflammation and cellular signals. In colorectal cancer (CRC) cells, PFKFB3 not only has the property of high expression, but also probably relate to inflammation-cancer transformation. Recent studies indicate that PFKFB3 is involved in chemoradiotherapy resistance as well, such as breast cancer, endometrial cancer and CRC. Cancer stem cells (CSCs) are self-renewable cell types that contribute to oncogenesis, metastasis and relapse. Several studies indicate that CSCs utilize glycolysis to fulfill their energetic and biosynthetic demands in order to maintain rapid proliferation and adapt to the tumor microenvironment changes. In addition, elevated PFKFB3 has been reported to correlate with self-renewal and metastatic outgrowth in numerous kinds of CSCs. This review summarizes our current understanding of PFKFB3 roles in modulating cancer metabolism to maintain cell proliferation and stemness, and discusses its feasibility as a potential target for the discovery of antineoplastic agents, especially in CRC.