Dataset Information

Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer.

ABSTRACT: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. AXL, which is a member of the receptor tyrosine kinases, has been established as a strong candidate for the targeted therapy of cancer. Therefore, the present study aimed to investigate the role of AXL in NSCLC; in particular the molecular mechanisms underlying the involvement of AXL in the epithelial-to-mesenchymal transition (EMT). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis demonstrated that AXL, EMT-inducing Twist and the mesenchymal marker N-cadherin were upregulated, and the epithelial markers E-cadherin and ?-cadherin were downregulated, in the PC9 NSCLC cell line. Furthermore, downregulation of AXL expression by RNA interference was shown to inhibit cell growth by inducing the apoptosis of PC9 cells, as demonstrated by MTT and flow cytometry analyses. Notably, inhibition of AXL attenuated the regulation of EMT-associated genes, specifically downregulating Twist and N-cadherin, and upregulating E-cadherin and ?-cadherin. Conversely, downregulation of Twist did not affect the expression levels of AXL. These results suggested that AXL may inhibit the EMT by the regulation of EMT-associated genes in the PC9 cell line. The results of the present study indicated that AXL may have a role in the regulation of EMT and the cell cycle of the PC9 cells; thus suggesting that AXL may have clinical significance in the design of therapeutic strategies targeting NSCLC and EMT signaling pathways.

SUBMITTER: Ying X

PROVIDER: S-EPMC5488737 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer.

Ying Xueming X Chen Jun J Huang Xueming X Huang Peng P Yan Shaocong S

Experimental and therapeutic medicine 20170601 1

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. AXL, which is a member of the receptor tyrosine kinases, has been established as a strong candidate for the targeted therapy of cancer. Therefore, the present study aimed to investigate the role of AXL in NSCLC; in particular the molecular mechanisms underlying the involvement of AXL in the epithelial-to-mesenchymal transition (EMT). Reverse transcription-quantitative polymerase chain rea ...[more]

PMID: 28673000

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Project description:The aim of the present study was to investigate whether miR‑203 can inhibit transforming growth factor‑β (TGF‑β)‑induced epithelial‑mesenchymal transition (EMT), and the migration and invasion ability of non‑small cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expression levels of miR‑203, SMAD3 mRNA and protein in NSCLC tissues were examined, as well as their corresponding paracancerous samples. The miR‑203 mimics and miR‑203 inhibitor were transfected into the H226 cell line. RT‑qPCR was used to assess the expression levels of E‑cadherin, Snail, N‑cadherin and vimentin mRNA, and western blotting was performed to detect the expression levels of p‑SMAD2, SMAD2, p‑SMAD3, SMAD3 and SMAD4. The cell migration and invasion abilities were detected by Transwell assays. The target site of SMAD3 was predicted by the combined action between miR‑203 and dual luciferase. The results revealed that the RNA levels of miR‑203, compared with paracancerous tissues, were decreased in NSCLC tissues, while SMAD3 mRNA and protein levels were upregulated, and miR‑203 inhibited SMAD3 expression. Induction of TGF‑β led to decreased E‑cadherin mRNA levels, upregulation of Snail, N‑cadherin and vimentin mRNA levels (P<0.05), and significant increase in cell migration and invasion, whereas transfection of miR‑203 mimics reversed the aforementioned results (P<0.05). Conversely, miR‑203 inhibitor could further aggravate the aforementioned results (P<0.05). Western blot results revealed that transfection of miR‑203 mimics significantly reduced the protein expression of SMAD3 and p‑SMAD3 (P<0.05). Furthermore, the results of the Dual‑Luciferase assay revealed that miR‑203 inhibited SMAD3 expression by interacting with specific regions of its 3'‑UTR. Overall, a novel mechanism is revealed, in which, miR‑203 can inhibit SMAD3 by interacting with specific regions of the 3'‑UTR of SMAD3, thereby restraining TGF‑β‑induced EMT progression and migration and invasion of NSCLC cells.

Project description:BackgroundMesenchymal-epithelial transition exon14 (METex14) skipping is one of the therapeutic driver oncogene mutations in non-small cell lung cancer (NSCLC), and can be treated with tepotinib and capmatinib. There is only one report on computed tomography (CT) findings of METex14 skipping-positive NSCLC, which shows that the primary tumor tends to have a large mass in the upper lobe, and extrathoracic metastases are common. This study examined the CT findings of METex14 skipping-positive NSCLC, focusing on the features of the margins and internal structures.MethodsWe consecutively included patients with METex14 skipping-positive NSCLC who were diagnosed between January 2018 and December 2020 at four independent institutions. We retrospectively reviewed the patient demographics and CT findings for tumor margins (invasion into surrounding tissue, lobulation, pleural indentation, spicula, and ground-glass opacity) and internal structures (air bronchograms, cavitation and internal low-density area).ResultsFifteen patients with METex14 skipping-positive NSCLC were identified. Almost half of the patients were men (7/15; 46.7%), and their median age was 75.0 years. More than half were either current or former smokers (9/15; 60.0%). A vast majority of histological subtypes were adenocarcinoma (10/15; 66.7%), followed by pleomorphic carcinoma (3/15; 20.0%) and squamous cell carcinoma (2/15; 13.3%). With regard to CT findings, most primary tumors presented as masses larger than 30 mm (12/15; 80.0%) and were located in the upper lobes (12/15; 80.0%). Invasion into surrounding tissue and presence of internal low-density areas were observed in 60.0% (9/15) and 66.7% (10/15) of the primary tumors, respectively. Additionally, their frequencies increased to 72.7% (8/11) and 90.9% (10/11) in stage III/IV cases, respectively. In lymph node metastasis, internal low-density areas were observed in 8/10 cases (80.0%). Although these two CT features were rarely observed in distant metastases at diagnosis, they became apparent with progression of the metastatic tumor size.ConclusionsMETex14 skipping-positive NSCLC tumors tend to invade surrounding tissue and possess internal low-density areas. These CT findings might be characteristic of METex14 skipping-positive NSCLC.

Dataset Information

Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer.

Publications

Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer.

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