Rebane-Klemm Egle, Reinsalu Leenu, Puurand Marju, Shevchuk Igor, Bogovskaja Jelena, Suurmaa Kulliki, Valvere Vahur, Moreno-Sanchez Rafael, Kaambre Tuuli
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
Department of Chemistry and Biotechnology, School of Science, Tallinn University of Technology, Tallinn, Estonia.
Front Oncol. 2023 Jun 5;13:1171887. doi: 10.3389/fonc.2023.1171887. eCollection 2023.
In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully obtained the glycolytic phenotype proposed by O. Warburg and rather depends on mitochondrial respiration. However, the pattern of metabolic adaptations during tumorigenesis is still unknown. Understanding the interplay between genetic and metabolic changes that initiate tumor development could provide biomarkers for diagnosing cancer early and targets for new cancer therapeutics. We used human CRC and polyp tissue material and performed high-resolution respirometry and qRT-PCR to detect changes on molecular and functional level with the goal of generally describing metabolic reprogramming during CRC development. Colon polyps were found to have a more glycolytic bioenergetic phenotype than tumors and normal tissues. This was supported by a greater , , , and expression. Despite the increased glycolytic activity, cells in polyps were still able to maintain a highly functional OXPHOS system. The mechanisms of OXPHOS regulation and the preferred substrates are currently unclear and would require further investigation. During polyp formation, intracellular energy transfer pathways become rearranged mainly by increasing the expression of mitochondrial adenylate kinase () and creatine kinase () isoforms. Decreased glycolysis and maintenance of OXPHOS activity, together with the downregulation of the CK system and the most common AK isoforms ( and ), seem to play a relevant role in CRC development.
在结直肠癌（CRC）能量代谢研究中，息肉的癌前阶段仍未得到充分探索。到目前为止，已经表明CRC尚未完全获得O. Warburg提出的糖酵解表型，而是相当依赖线粒体呼吸作用。然而，肿瘤发生过程中的代谢适应模式仍然未知。了解启动肿瘤发展的遗传和代谢变化之间的相互作用，可以为早期诊断癌症提供生物标志物，并为新的癌症治疗提供靶点。我们使用人类CRC和息肉组织材料，进行了高分辨率呼吸测定和qRT-PCR，以检测分子和功能水平的变化，目的是总体描述CRC发展过程中的代谢重编程。发现结肠息肉比肿瘤和正常组织具有更明显的糖酵解生物能量表型。这得到了更高的[具体物质1]、[具体物质2]、[具体物质3]和[具体物质4]表达的支持。尽管糖酵解活性增加，但息肉中的细胞仍然能够维持高度功能性的氧化磷酸化（OXPHOS）系统。目前尚不清楚OXPHOS调节机制和首选底物，这需要进一步研究。在息肉形成过程中，细胞内能量转移途径主要通过增加线粒体腺苷酸激酶（[具体英文缩写1]）和肌酸激酶（[具体英文缩写2]）同工型的表达而重新排列。糖酵解减少和OXPHOS活性维持，以及CK系统和最常见的AK同工型（[具体同工型1]和[具体同工型2]）的下调，似乎在CRC发展中起相关作用。
