ETV4 overexpression promotes progression of non–small cell lung cancer by upregulating PXN and MMP1 transcriptionally

Abstract

ETS variant 4 (ETV4), together with ETV1 and ETV5, constitute the PEA3 subfamily of ETS transcription factors, which are implicated in the progression of many cancers.However, the clinicopathologic significance and molecular events regulated by ETV4 in lung cancer are still poorly understood, especially in squamous cell carcinoma of the lung. Here, we aimed to identify functional targets involved in ETV4-driven lung tumorigenesis. Microarray analysis and validation data revealed that ETV4 was the most preponderant PEA3 factor, which was significantly related to the advanced stage, lymph node metastasis, and poor prognosis of non-small cell lung cancers (NSCLCs; all P < .001). Reduced ETV4 expression suppressed the growth and metastasis of NSCLC both in vivo and in vitro. Microarray, gain, or loss of function and luciferase report assays revealed the direct regulatory effect of ETV4 on the expression of focal adhesion gene PXN and matrix metalloproteinase 1 (MMP1), and PXN and/or MMP1 inhibition partially abolished cell proliferation and migration induced by ETV4. Kaplan-Meier analysis indicated that ETV4 and PXN or MMP1 cooverexpression is associated with poor prognosis in human NSCLCs. In conclusion, the ETV4-PXN and ETV4-MMP1 axes are useful biomarkers of tumor progression and worse outcomes in NSCLCs. K E Y W O R D S ETV4, non-small cell lung cancer, prognosis, PXN

Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis

“…Arraystar Human LncRNA Microarray V4.0 (Kangchen BioTech Co., Ltd.) was used to screen the global profiling of human lncRNAs and protein-coding transcripts. The samples included eight frozen tissues of NSCLCs (four samples of squamous cell carcinoma and four of adenocarcinoma) and paired normal lung tissues (GSE137445)(26). The total RNA was extracted from the cells or tissues as aforementioned.…”

Identification of potential diagnostic biomarkers in MMPs for pancreatic carcinoma

“…Overexpression of ETV4 promotes progression, proliferation and invasion of many carcinomas. [ 43 , 69 , 70 ] STAT3 regulates glycolysis in hepatocellular carcinoma cells, [ 71 ] is associated with inhibition of epithelial-mesenchymal transition inhepatocellular carcinoma, [ 72 ] and is related to proliferation promotion and apoptosis inhibition in esophageal squamous cell carcinoma. [ 73 , 74 ] Previous studies have also identified a role for STAT3 in the regulation of PC.…”

ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma

“…For instance, ETV4 has been documented to be necessary for the activation of the estrogen signaling and proliferation of endometrial cancer cells (Rodriguez et al, 2020). As a transcription factor, it transcriptionally activated the paxillin (PXN) and matrix metalloproteinase 1 (MMP1) and promoted the progression of non–small cell lung cancer (Wang et al, 2020). Similar oncogenic mediations by ETV4 have been observed in malignancies, such as breast cancer (Dumortier et al, 2018), gastric cancer (Cai et al, 2020), and pancreatic cells (Tyagi et al, 2018).…”

“…It is well accepted that COAD is caused by genetic and epigenetic changes. ETS variant 4 (ETV4), ETV1, and ETV5 constitute the PEA3 subfamily of ETS transcription factors, which are frequently involved in the pathogenesis of many cancers (Wang et al, 2020). The PEA3 family factors are oncogenic transcription factors whose overexpression induces proliferation and invasiveness of cancer cells via triggering transcription of cell division‐ and migration‐related genes (Oh et al, 2012).…”