Tastin promotes non-small-cell lung cancer progression through the ErbB4, PI3K/AKT, and ERK1/2 pathways

Abstract

Tastin might be involved in tumorigenesis, but its role in non-small-cell lung cancer (NSCLC) has not been adequately explored. This work aimed to examine tastin’s role in NSCLC and to explore the underlying mechanism. The Gene Expression Omnibus (GEO), Gene Expression Database of Normal and Tumor tissues (GENT), and Cancer Genome Atlas (TCGA) databases were used. Four GEO datasets (GSE81089, GSE40419, GSE74706, and GSE19188) containing gene expression data for NSCLC and normal tissue samples were analyzed for tastin mRNA expression. Tastin expression levels in different tissues were compared using the GENT website. TCGA biolinks were used to download gene expression quantification ( n = 594) and overall survival data ( n = 535). In total, 30 lung adenocarcinoma and 25 lung squamous cell carcinoma cases were enrolled. In addition, four-week-old male BALB/c nude mice ( n = 9/group) were used to establish xenograft mouse models. Furthermore, cultured HEK293T, A549, and NCI-H226 cells assessed. Immunoblot, hematoxylin and eosin (H&E) staining, immunohistochemistry, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), fluorescence microscopy, flow cytometry, lentiviral transduction, and MTT, colony formation, wound healing, and Transwell assays were carried out. Tastin expression levels were markedly increased in NSCLC tumor tissue specimens and correlated with a poorer prognosis. Silencing of tastin inhibited the proliferative and migratory abilities of NSCLC cells. Bioinformatic analysis suggested that tastin interacts with ErbB4. The PI3K/AKT and ERK1/2 downstream pathways were suppressed in tastin-deficient cells. In conclusion, tastin might be involved in NSCLC growth and invasion and is a potential therapeutic target in NSCLC.

Bidirectional Mendelian randomization analysis of the genetic association between primary lung cancer and colorectal cancer

“…To investigate the underlying reasons, a PLC GWAS conducted by James et al in 2017 demonstrated significant genomic differences between LUAD and LUSC, despite both belonging to NSCLC, suggesting potential distinct mechanisms for the development of LUAD and LUSC [ 13 ]. Furthermore, multiple previous studies have indicated the presence of shared signaling pathways, such as the PI3K pathway [ 40 , 41 ], FGFR1 pathway [ 42 , 43 ] between LUSC and CRC, implying potential common genetic origins and developmental processes between these two cancer types.…”

Insights from the protein interaction Universe of the multifunctional “Goldilocks” kinase DYRK1A

“…While it was found to be pro-tumorigenic and associated with poor prognosis in most cancer types, including glioma, lung, breast, ovarian, colorectal, gastric and prostate cancer ( Li K. et al, 2019 ; Jin et al, 2020 ; Zhao et al, 2021 ; Liu H. et al, 2022 ; Li et al, 2022 ; Wang et al, 2023 ; Yue et al, 2023 ), some studies suggest that high expression of TROAP could predict better survival in acute myeloid leukemia ( He et al, 2023 ). The tumor-promoting role of TROAP has been experimentally validated in several preclinical cancer models, including breast, kidney, liver, and prostate cancer ( Li K. et al, 2019 ; Jin et al, 2020 ; Li L. et al, 2021 ; Wang et al, 2023 ; Yue et al, 2023 ). Mechanistically, the depletion of TROAP was found to cause cell cycle arrest and inhibition of multiple cancer growth-promoting pathways.…”

Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway

“…The experimental procedure was performed as previously described in the previous study. 32 The total protein concentrations of the cells and tissues were measured using the BCA protein quantification method (Beyotime, China). Equal amounts of protein were resolved by electrophoresis on a 10% sodium dodecyl-sulfate (SDS) gel and then transferred onto nitrocellulose membranes.…”