NRP1 regulates radiation-induced EMT via TGF-β/Smad signaling in lung adenocarcinoma cells

Abstract

Purpose: Radiation has been shown to promote the epithelial-mesenchymal transition (EMT) in tumor cells, and TGF-b/Smad and PI3K-Akt signaling pathways play an important role in the EMT. In this study, we investigated the effects of neuropilin-1 (NRP1) on radiation-induced TGF-b/Smad and non-classical Smad signaling pathways in lung cancer cells, as well as the effects of NRP1 on invasion and migration. Materials and methods: Changes in the expression levels of EMT markers (b-catenin, N-cadherin, and vimentin) and related transcription factors (Twist and ZEB1) in stably transfected cells were detected by Western blotting and qPCR, and changes were assessed by TGF-b/Smad and non-classical Smad signaling. Immunofluorescence was used to detect the expression of the cytoskeletal protein F-actin. Expression of TGF-b1 and CXCL-12 was detected by ELISA. Transwell and scratch assays were used to detect the invasive ability and migration of lung cancer cells, respectively. Results: Our results showed that ionizing radiation could induce the EMT as well as morphological changes in lung adenocarcinoma cells (A549); however, the effects were not significant in lung squamous carcinoma cells (SK-MES-1). Moreover, we showed that NRP1 promotes the EMT induced by ionizing radiation in A549 cells, which may be related to the increased expression of EMT-related transcription factors. NRP1 may promote the radiation-induced EMT of A549 cells mainly through TGF-b1/Smad2/3 signaling. NRP1 also enhanced radiation-induced invasion, migration, and CXCL-12 expression in A549 cells. Conclusions: We conclude that NRP1 promotes radiation-induced EMT in lung adenocarcinoma cells via TGF-b1/Smad signaling and not non-classical Smad signaling, and enhances the invasion and migration of lung adenocarcinoma cells.

KLF8 is activated by TGF‐β1 via Smad2 and contributes to ovarian cancer progression

“…Neuropilin-1 may promote EMT induced by radiation via TGF-β1/Smad2/3 signaling in lung cancer cells and thus enhance invasion and migration. 27 Furthermore, we knocked down Smad2 in OC cells to explore whether TGF-β1 treatment-induced changes in the EMT markers such as E-cadherin and vimentin expression in OC cells occurred through the KLF8/ Smad2 axis. Our findings indicate that expression of E-cadherin was increased, KLF8 and vimentin expression was reduced in Smad2-deficient cells, and TGF-β1 induction failed to induce KLF8 expression and EMT in Smad2-deficient cells.…”

“…Several other studies reported TGF‐β1‐induced EMT transcription and regulation of E‐cadherin, vimentin, N ‐cadherin, Snail, and support cancer progression. Neuropilin‐1 may promote EMT induced by radiation via TGF‐β1/Smad2/3 signaling in lung cancer cells and thus enhance invasion and migration 27 …”

A 25 Immune-Related Gene Pair Signature Predicts Overall Survival in Cervical Cancer

“…19 In addition, Nrp1 is reported as a new tumor marker in hepatocellular carcinoma 20 ; it also regulates gastric cancer progression 21 and enhances the invasive and migratory properties of lung adenocarcinoma cells. 22 The INHBA gene plays an important role in many tumors, with high INHBA levels in esophageal squamous cell carcinoma and other solid tumors reflecting poor prognosis. 23 Moreover, INHBA overexpression results in poor clinical outcomes in bladder urothelial carcinoma, indicating its potential as a prognostic marker and a new therapeutic target.…”

Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549

“…The sensitivity of cells to ionizing radiation determines the efficacy of radiotherapy, and the inherent radioresistant ability of tumour cells further limits the use of radiotherapy (3). NRP1 can enhance the radiation resistance of tumours (8,9,30,31). Previous studies have shown that the expression of NRP1 significantly increases with increasing radiation dose.…”