FUT2 Facilitates Autophagy and Suppresses Apoptosis via p53 and JNK Signaling in Lung Adenocarcinoma Cells

Abstract

Lung cancer is the most common cancer with high morbidity and mortality worldwide. Our previous studies showed that fucosyltransferase 2 (FUT2) is highly expressed in lung adenocarcinoma (LUAD) and plays a vital role in the tumorigenesis of LUAD. However, the underlying mechanism is not fully understood. Autophagy has recently attracted increasing attention due to its pro-survival role in cancer progression and metastasis. Here, we found that FUT2 was up-regulated and had an AUC (Area Under Curve) value of 0.964 in lung adenocarcinoma based on the TCGA dataset. Knockdown of FUT2 weakened the autophagy response, as evidenced by a degradation of LC3-II and Beclin1. The phosphorylation levels of AMPK, ULK1, and PI3K III were significantly reduced by FUT2 knockdown. FUT2 promoted the translocation of p53 from the cytoplasm into the nucleus, which triggered the DRAM1 pathway and enhanced autophagy. Meanwhile, the knockdown of FUT2 increased the phosphorylation of JNK and promoted mitochondrial-mediated apoptosis. Furthermore, the knockdown of FUT2 inhibited the autophagy induced by Z-VAD-FMK and promoted the apoptosis suppressed by rapamycin. The autophagy and apoptosis regulated by FUT2 antagonized each other. Taken together, these findings provide a mechanistic understanding of how FUT2 mediated the crosstalk between autophagy and apoptosis, which determine lung cancer cell death and survival, leading to the progression of lung adenocarcinoma.

Construction of a prognostic model based on memory CD4+ T cell–associated genes for lung adenocarcinoma and its applications in immunotherapy

“…35 The tumor suppressor p53 and its associated p53 signaling pathway have been implicated in mediating the progression of various cancers such as breast cancer, 36 pancreatic cancer, 37 and lung cancer. 38 The study by Zhang et al 39 found that activation of the p53 signaling pathway can effectively promote autophagy in LUAD cells and inhibit apoptosis of cancer cells. Glutamine is a conditionally essential amino acid crucial for cancer cells.…”

“… 38 The study by Zhang et al. 39 found that activation of the p53 signaling pathway can effectively promote autophagy in LUAD cells and inhibit apoptosis of cancer cells. Glutamine is a conditionally essential amino acid crucial for cancer cells.…”

Targeting protein glycosylation to regulate inflammation in the respiratory tract: novel diagnostic and therapeutic candidates for chronic respiratory diseases

“…FUT1 expression has been correlated with treatment outcomes in LUAD patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ( 73 ). FUT2 is overexpressed in LUAD and may facilitate autophagy and suppress apoptosis via the p53 and JNK pathways ( 74 ), as well as induce EMT through TGF-β/Smad signaling in LUAD ( 75 ). FUT4 expression shows a negative correlation with the overall survival in operable LUAD ( 113 , 114 ), and may induce lung colonization and distant metastases of lung cancer cells ( 114 ).…”

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis

“…The top genes that correlated with histologic severity (Nancy score 35 ) included proinflammatory genes SAA1, S100A8, S100A9; myeloid cell-associated genes TREM1, LILRA5; neutrophil chemotactic genes FPR1, FPR2, CXCL1, CXCR1, CXCR2, FCGR3B/CD16; hypoxia related gene HIF1A; autophagy gene DRAM1 and unfolded protein response gene XBP1 (Fig. 1i) [36][37][38][39] .The findings from our EC-bulk transcriptomic data revealed a complex, myeloid cell-dominated milieu in UCassociated inflammation that significantly correlated with parameters of clinical, endoscopic, and histologic severity.…”