Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China.
Adv Sci (Weinh). 2024 Sep;11(35):e2400227. doi: 10.1002/advs.202400227. Epub 2024 Jul 17.
Lysine lactylation (Kla) plays a vital role in several physiological processes. However, the cancer-specific modulation of Kla in gastrointestinal (GI) tumors requires systematic elucidation. Here, global lactylome profiling of cancerous and adjacent tissues is conducted from 40 patients with GI cancer and identified 11698 Kla sites. Lactylome integration revealed that Kla affects proteins involved in hallmark cancer processes, including epigenetic rewiring, metabolic perturbations, and genome instability. Moreover, the study revealed pan-cancer patterns of Kla alterations, among which 37 Kla sites are consistently upregulated in all four GI cancers and are involved in gene regulation. It is further verified that lactylation of CBX3 at K10 mediates its interaction of CBX3 with the epigenetic marker H3K9me3 and facilitates GI cancer progression. Overall, this study provides an invaluable resource for understanding the lactylome landscape in GI cancers, which may provide new paths for drug discovery for these devastating diseases.
赖氨酸酰化（Kla）在许多生理过程中起着至关重要的作用。然而，胃肠道（GI）肿瘤中 Kla 的癌症特异性调节需要系统地阐明。在这里，对 40 名 GI 癌症患者的癌症和相邻组织进行了全乳酰组谱分析，鉴定了 11698 个 Kla 位点。乳酰组整合表明，Kla 影响涉及标志性癌症过程的蛋白质，包括表观遗传重排、代谢扰动和基因组不稳定性。此外，该研究揭示了 Kla 改变的泛癌模式，其中 37 个 Kla 位点在所有四种 GI 癌症中均一致上调，并且涉及基因调控。进一步验证了 CBX3 在 K10 处的乳酰化介导了其与表观遗传标记 H3K9me3 的相互作用，并促进了 GI 癌症的进展。总的来说，这项研究为理解 GI 癌症中的乳酰组图谱提供了宝贵的资源，这可能为这些毁灭性疾病的药物发现提供新的途径。
