Cancer cells undergo metabolic reprogramming to sustain their own survival under an environment of increased energy demand; however, the mechanism by which cancer cells ensure survival under glucose deprivation stressed conditions remains elusive. Here, we show that deprivation of glucose, dramatically activated the glycogen pathway, accompanied by elevated phosphoglucomutase 1 (PGM1) expression. We further identified that AMP-activated protein kinase (AMPK) stimulated PGM1 expression by inducing histone deacetylase 8 (HDAC8) phosphorylation. Moreover, we demonstrated that glucose deprivation-induced AMPK activation stimulated the translocation of HDAC8 from the nucleus to the cytoplasm, consequently disrupting the binding between HDAC8 and histone 3. PGM1 expression was also found to be critical for lung cancer glycolysis, the oxidative pentose phosphate pathway, and oxidative phosphorylation under glucose deprivation conditions, and further led to the aberrant expression of metabolic enzymes involved in glucose metabolism mediated by ERK1/2. Finally, PGM1 was found to be highly expressed in lung cancer tissues from patients, which correlated with a poor prognosis. Taken together, these results revealed that AMPK activation by glucose deprivation leads to enhanced PGM1 expression, an essential component of the metabolic switch, to facilitate cancer progression, suggesting PGM1 as promising anti-cancer treatment targets.

癌细胞经过代谢重编程以在能量需求增加的环境下维持自身生存；然而，癌细胞在葡萄糖缺乏应激条件下确保存活的机制仍然难以捉摸。在这里，我们显示葡萄糖的剥夺显着激活了糖原途径，并伴有磷酸化葡萄糖突变酶1（PGM1）表达的升高。我们进一步确定，AMP激活的蛋白激酶（AMPK）通过诱导组蛋白脱乙酰基酶8（HDAC8）磷酸化刺激PGM1表达。此外，我们证明了葡萄糖剥夺诱导的AMPK激活刺激了HDAC8从细胞核到细胞质的转运，因此破坏了HDAC8和组蛋白3的结合。PGM1表达也被发现对肺癌糖酵解至关重要，氧化戊糖磷酸途径，以及葡萄糖剥夺条件下的氧化磷酸化作用，进一步导致由ERK1 / 2介导的参与葡萄糖代谢的代谢酶异常表达。最后，发现PGM1在患者的肺癌组织中高表达，这与预后不良有关。综上所述，这些结果表明，葡萄糖剥夺引起的AMPK激活导致PGM1表达增强，这是代谢转换的重要组成部分，促进了癌症的进展，提示PGM1是有希望的抗癌治疗靶点。发现PGM1在患者的肺癌组织中高表达，这与不良预后相关。综上所述，这些结果表明，葡萄糖剥夺引起的AMPK激活导致PGM1表达增强，这是代谢转换的重要组成部分，促进了癌症的进展，提示PGM1是有希望的抗癌治疗靶点。发现PGM1在患者的肺癌组织中高表达，这与不良预后相关。综上所述，这些结果表明，葡萄糖剥夺引起的AMPK激活导致PGM1表达增强（这是代谢转换的重要组成部分），从而促进了癌症的进展，表明PGM1是有前途的抗癌治疗靶点。