Pim1 supports human colorectal cancer growth during glucose deprivation by enhancing the Warburg effect

Summary

Cancer cells metabolize glucose mainly by glycolysis and are well adapted to metabolic stress. Pim1 is an oncogene that promotes colorectal cancer (CRC) growth and metastasis, and its expression is positively correlated with CRC progression. However, the mechanism underlying Pim1 overexpression during CRC progression and the role of Pim1 in CRC metabolism remains unclear. In this study, we discovered that Pim1 expression was significantly upregulated in response to glucose deprivation-induced metabolic stress via AMPK signaling. Pim1 promoted CRC cell proliferation in vitro and tumorigenicity in vivo. Clinical observations demonstrated that Pim1 expression was higher in CRC tissues than in adjacent normal tissues. Pim1 overexpression in CRC tissues not only predicted CRC prognosis in patients but also exhibited a positive relationship with ¹⁸F-FDG uptake. Further in vitro experiments demonstrated that Pim1 promoted the Warburg effect and that Pim1 expression was positively correlated with HK2 and LDHA expression. Pim1-silenced cells were more vulnerable to glucose starvation, and Pim1 induced tumor proliferation or tolerance to glucose starvation was attenuated by the block of Warburg effect. In conclusion, glucose deprivation is one of the mechanisms that lead to elevated Pim1 expression in CRC, and Pim1 upregulation ensures CRC growth in response to glucose deprivation by facilitating the Warburg effect in a compensatory manner.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FzQSPr