Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

P300 acts as a transcription coactivator and an acetyltransferase that plays an important role in tumourigenesis and progression. In previous studies, it has been confirmed that p300 is an important regulator in regulating the evolution of malignant tumours and it also has extensive functions. From the perspective of non-posttranslational modification, it has been proven that p300 can participate in regulating many pathophysiological processes, such as activating oncogene transcription, promoting tumour cell growth, inducing apoptosis, regulating immune function and affecting embryo development. In recent years, p300 has been found to act as an acetyltransferase that catalyses a variety of protein modification types, such as acetylation, propanylation, butyylation, 2-hydroxyisobutyration, and lactylation. Under the catalysis of this acetyltransferase, it plays its crucial tumourigenic driving role in many malignant tumours. Therefore, the function of p300 acetyltransferase has gradually become a research hotspot. From a posttranslational modification perspective, p300 is involved in the activation of multiple transcription factors and additional processes that promote malignant biological behaviours, such as tumour cell proliferation, migration, and invasion, as well as tumour cell apoptosis, drug resistance, and metabolism. Inhibitors of p300 have been developed and are expected to become novel anticancer drugs for several malignancies. We review the characteristics of the p300 protein and its functional role in tumour from the posttranslational modification perspective, as well as the current status of p300-related inhibitor research, with a view to gaining a comprehensive understanding of p300.

Lung cancer is the most common malignant tumor and the leading cause of cancer-related deaths worldwide. Because current treatments for advanced non-small cell lung cancer (NSCLC), the most prevalent lung cancer histological subtype, show limited efficacy, screening for tumor-associated biomarkers using bioinformatics reflects the hope to improve early diagnosis and prognosis assessment. In our study, a Gene Expression Omnibus dataset was analyzed to identify genes with prognostic significance in NSCLC. Upon comparison with matched normal tissues, 118 differentially expressed genes (DEGs) were identified in NSCLC, and their functions were explored through bioinformatics analyses. The most significantly upregulated DEGs were TOP2A, SLC2A1, TPX2, and ASPM, all of which were significantly associated with poor overall survival (OS). Further analysis revealed that TOP2A had prognostic significance in early-stage lung cancer patients, and its expression correlated with levels of immune cell infiltration, especially dendritic cells (DCs). Our study provides a dataset of potentially prognostic NSCLC biomarkers, and highlights TOP2A as a valuable survival biomarker to improve prediction of prognosis in NSCLC.

Combination of CALR and PDIA3 is a potential prognostic biomarker for non-small cell lung cancer Combination of CALR and PDIA3 is a potential prognostic biomarker for non-small cell lung cancer

Aberrant protein post-translational modification is a hallmark of malignant tumors. Lysine succinylation (Ksucc) plays a vital role in cell energy metabolism in various cancers. However, whether succinylation can be catalyzed by acetyltransferase p300 remains unclear. In this study, we unveiled that p300 is a “writer” for succinylation, and p300-mediated Ksucc promotes cell glycometabolism in lung adenocarcinoma (LUAD). Specifically, our succinylome data revealed that EP300 deficiency leads to the systemic reduction of Ksucc, and 79.55% of the p300-succinylated proteins were found in the cytoplasm, which were primarily enriched in the carbohydrate metabolism process. Interestingly, deleting EP300 led to a notable decrease in Ksucc levels on several glycolytic enzymes, especially Phosphoglycerate Kinase 1 (PGK1). Mutation of the succinylated site of PGK1 notably hindered cell glycolysis and lactic acid excretion. Metabolomics in vivo indicated that p300-caused metabolic reprogramming was mainly attributed to the altered carbohydrate metabolism. In addition, 89.35% of LUAD patients exhibited cytoplasmic localization of p300, with higher levels in tumor tissues than adjacent normal tissues. High levels of p300 correlated with advanced tumor stages and poor prognosis of LUAD patients. Briefly, we disclose the activity of p300 to catalyze succinylation, which contributes to cell glucose metabolic reprogramming and malignant progression of lung cancer.

Patient behavior and physiology can directly affect cancer metabolism. Smoking is the leading risk factor for non-small cell lung cancer (NSCLC). Here, we identified that smoking modulates lung cancer cell metabolism through altered protein post-translational modification. Proteomic analyses identified elevated K251 succinylation (K251-Su) of GAPDH, a key enzyme in glycolysis, in NSCLC samples, and GAPDH K251-Su was significantly higher in patients who smoke compared to non-smokers. Exposure of lung cancer cells to cigarette smoke extract led to increased uptake of glutamine and enhanced GAPDH K251-Su. Glutamine uptake by cancer cells in hypoxic and nutrient-deficient microenvironments provided succinyl-CoA donors for GAPDH succinylation at K251, which was catalyzed by acyltransferase p300. K251-Su increased GAPDH stability by suppressing TRIM4-mediated K254 ubiquitination. GAPDH K251-Su enhanced glycolysis and glutamine reductive carboxylation to meet the demands for cell growth and to support survival in hypoxic and nutrient-depleted conditions, promoting tumor growth and metastasis. These findings indicate that tobacco smoking mediates metabolic reprogramming of cancer cells through succinylation of GAPDH to drive NSCLC progression.