Panoply™ Human PIM1 Knockdown Stable Cell Line

Cancer cells primarily metabolize glucose through glycolysis and are highly adaptable to metabolic stress. Pim1 is an oncogene that promotes the growth and metastasis of colorectal cancer (CRC), and its expression level is positively correlated with CRC progression. However, the mechanisms underlying Pim1 overexpression during CRC progression and the role of Pim1 in CRC metabolism remain unclear. Here, researchers found that Pim1 expression was significantly upregulated under glucose deprivation-induced metabolic stress, a process mediated by the AMP-activated protein kinase signaling pathway. Pim1 promoted CRC cell proliferation in vitro and tumorigenesis in vivo. Clinical observations showed that Pim1 expression levels were higher in CRC tissues than in adjacent normal tissues. Overexpression of Pim1 in CRC tissues not only predicted patient prognosis but was also positively correlated with 18F-fluorodeoxyglucose uptake. Further in vitro experiments showed that Pim1 promoted the Warburg effect, and Pim1 expression was positively correlated with the expression of hexokinase 2 and lactate dehydrogenase A. Pim1-silenced cells were more sensitive to glucose starvation, while blocking the Warburg effect attenuated Pim1-induced tumor proliferation or tolerance to glucose starvation. In summary, glucose deprivation is one of the mechanisms leading to elevated Pim1 expression in CRC, and the upregulation of Pim1 compensates by promoting the Warburg effect, ensuring that CRC continues to grow under glucose deprivation conditions.

To investigate the effect of Pim1 on tumor cell proliferation, researchers performed a CCK8 assay. Cell proliferation was inhibited in Pim1-knockdown RKO and LOVO cells (Figure 1A). Conversely, the growth rate of Pim1-overexpressing HT29 cells was significantly higher than that of control HT29 cells (Figure 1A). Colony formation assays showed that, compared to the control group, Pim1 knockdown inhibited colony formation in RKO and LOVO cells, while Pim1 overexpression promoted colony formation (Figure 1B). To further validate the in vitro observations, researchers subcutaneously injected Pim1-knockdown RKO cells and control cells into nude mice. Consistent with the in vitro results, the tumor volume and weight of tumors formed by Pim1-knockdown RKO cells were significantly lower than those formed by control cells (Figure 1C). The Ki-67 index in the Pim1-knockdown group was also lower than that in the control group (Figure 1D). Therefore, Pim1 promotes the development and progression of colorectal cancer both in vitro and in vivo.

Figure 1. Pim1 promotes colorectal cancer cell proliferation in vitro and in vivo. (Zhang M, et al., 2018)