Recent advancements in cancer biology field suggest that glucose metabolism is a potential target for cancer treatment. However, little if anything is known about the metabolic profile of cancer stem cells (CSCs) and the related underlying mechanisms. The metabolic phenotype in lung CSC was first investigated. The role of collagen XVII, a putative stem cell or CSC candidate marker, in regulating metabolic reprogramming in lung CSC was subsequently studied. Through screening the genes involved in glycolysis, we identified the downstream targets of collagen XVII that were involved in metabolic reprogramming of lung CSCs. Collagen XVII and its downstream targets were then used to predict the prognosis of lung cancer patients. We showed that an aberrant upregulation of glycolysis and oxidative phosphorylation in lung CSCs is associated with the maintenance of CSC-like features, since blocking glycolysis and oxidative phosphorylation reduces sphere formation, chemoresistance, and tumorigenicity. We also showed that the Oct4-hexokinase 2 (HK2) pathway activated by collagen XVII-laminin-332 through FAK-PI3K/AKT-GSB3β/β-catenin activation induced the upregulation of glycolysis and maintenance of CSC-like features. Finally, we showed that collagen XVII, Oct4, and HK2 could be valuable markers to predict the prognosis of lung cancer patients. These data suggest the Oct4-HK2 pathway regulated by collagen XVII plays an important role in metabolic reprogramming and maintenance of CSC-like features in lung CSCs, which may aid in the development of new strategies in cancer treatment.

中文翻译：

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XVII胶原参与肺癌干细胞的多能性基因表达和代谢重编程

癌症生物学领域的最新进展表明，葡萄糖代谢是癌症治疗的潜在目标。但是，关于癌症干细胞（CSCs）的代谢特征及其相关的潜在机制知之甚少。首先研究了肺CSC中的代谢表型。随后研究了胶原XVII（一种推定的干细胞或CSC候选标记）在调节肺CSC的代谢重编程中的作用。通过筛选参与糖酵解的基因，我们确定了参与肺CSC代谢重编程的XVII胶原蛋白的下游靶标。然后使用胶原蛋白XVII及其下游靶标预测肺癌患者的预后。我们表明，肺CSCs中糖酵解和氧化磷酸化异常上调与维持CSC样功能有关，因为阻断糖酵解和氧化磷酸化减少了球的形成，化学抗性和致瘤性。我们还表明，胶原蛋白XVII-laminin-332通过FAK-PI3K /AKT-GSB3β/β-catenin激活激活的Oct4-己糖激酶2（HK2）途径诱导了糖酵解的上调和CSC样特征的维持。最后，我们表明胶原蛋白XVII，Oct4和HK2可能是预测肺癌患者预后的有价值的标志物。这些数据表明，胶原XVII调节的Oct4-HK2途径在代谢重编程和维持肺CSC中CSC样特征方面起着重要作用，