Luciferase Stable Cell Line - HT29

Hypoxia and glucose deficiency are common features in the microenvironment of solid tumors. Researchers previously found that the Acss2/HIF-2 signaling pathway affects tumor growth and metastasis by coordinating important genetic regulators including acetate-dependent acetyl coenzyme A synthase 2 (Acss2), CREB-binding protein (Cbp), Sirtuin 1 (Sirt1), and hypoxia-inducible factor 2 alpha (HIF-2α). In mouse experiments, exogenous acetic acid promotes the growth and metastasis of lateral abdominal tumors derived from fibrosarcoma HT1080 cells, a process dependent on the Acss2/HIF-2 pathway. Because colon epithelial cells have the highest concentration of acetic acid in vivo, the researchers hypothesized that colon cancer cells may also respond to the growth-promoting effects of acetic acid. It was found that in two human colon cancer cell lines, HCT116 and HT29, Acss2/HIF-2 signaling was activated in the absence of oxygen or glucose and was critical for clone formation, migration, and invasion in cell culture. Furthermore, HCT116- and HT29-derived lateral abdominal tumors grew faster in mice when supplemented with exogenous acetic acid, a process dependent on the Acss2/HIF-2 signaling pathway. Ultimately, Acss2 was predominantly localized in the nucleus in human colon cancer samples, consistent with its signaling role. Therefore, targeted inhibition of Acss2/HIF-2 signaling may have synergistic therapeutic effects in some colon cancer patients.

Figure 1. The researchers evaluated primary tumor weight and metastatic burden in mice bearing HT29-derived tumors treated with acetate or other short-chain fatty acids. Their findings reveal that acetate significantly enhances tumor growth and metastasis in an Acss2/HIF-2α-dependent manner, as evidenced by the luciferase activity measured in both control and knockdown HT29 cells. (Garcia JA, et al., 2023)