Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Abstract

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next‐generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up‐regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC‐1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.

Multifactoriality of Parkinson’s Disease as Explored Through Human Neural Stem Cells and Their Transplantation in Middle-Aged Parkinsonian Mice

“…Cancer and diabetes mellitus, one of the most common endocrine system disorders, have been shown to have pathogenic overlaps with PD, thus the involvement of the same proteins in PD and these two prevalent diseases ( Khwanraj et al, 2016 ; Sergi et al, 2019 ). Notably, the proteins which had the biggest fold change in differentiated hVM1 clone 32 cells, GAP43, DCLK1, and EEF1A2, are implicated in several cancers ( Patel et al, 2016 ; Giudici et al, 2019 ; Zheng et al, 2019 ).…”

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

“…AKT, as a key component in PI3K-AKT signaling, mediates PC progression (18)(19)(20). The relationship between UBE2C and EMT induction, which is also integral to metastatic tumor progression (18)(19)(20)(21)(22)(23)(24), was further analyzed, although no relationship between the two was identified. Further analyses revealed a strong association between Akt activation and the expression of UBE2C.…”

Association of Polygenetic Risk Scores Related to Cell Differentiation and Inflammation with Thyroid Cancer Risk and Genetic Interaction with Dietary Intake

“…This finding agrees with Italian, Icelandic, American, Dutch, Spanish, and Polish studies, which reported DIRC3 rs6759952 showed the strongest association with thyroid cancer in adults [ 12 , 23 ] GAP43 is a membrane phosphor protein that plays an integrative function in the brain and is expressed at high levels in the developing brain. GAP43 also promotes thyroid cancer tumorigenesis and tumor progression [ 24 ]. However, no study has yet demonstrated an association between GAP43 SNPs and thyroid cancer.…”