TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer

Abstract

Background Metastasis contributes to the high mortality rate of non-small cell lung cancer (NSCLC), and gaining a better understanding of its metastatic mechanisms would aid in initiating effective clinical treatment. Material/Method In this study, bioinformatics analyses of the GEO database and TCGA-LUAD were first used to identify the key node gene regulating NSCLC malignant progression. Further in vitro experiments, including wound healing assay, invasion assay, Western blot assay, and luciferase report assay, were used to clarify the functions and mechanism of TPX2 in NSCLC. Results Results of the TCGA analysis showed that TPX2 was significantly positively correlated with tumor metastasis and growth and the clinical stage of NSCLC. In addition, high levels of TPX2 significantly indicated a poor survival rate. In vitro experimental results also revealed that the upregulation of TPX2 significantly promoted NSCLC cell migration and invasion and could affect cell replasticity. Further results indicated that TPX2 significantly activated the epithelial-mesenchymal transition process and promoted the expression and activities of matrix metalloproteinase (MMP)2 and MMP9. Conclusions This study demonstrated that TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC.

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

“…Our results indicated that TPX2 promoted the cytoplasmic migration of ETS-1, which not only expands our understanding of the regulation mechanism of transcription factor activity, but also deepens our understanding of the cytoskeleton affecting the activity of cell signaling pathways. Some previous data showed that TPX2 could promote the invasion of cancerous cells by enhancing the expression of MMPs and our data provided a promising mechanism of TPX2's effect on MMPs (12,13).…”

“…A high level of TPX2 has been detected in several kinds of human cancer, such as bladder cancer, breast cancer, HCC, and especially prostate cancer (9,10). Previous research has focused on the role of TPX2 in centrosome formation and cell mitosis, and TPX2 is closely related to microtubules (11,12). The microtubule system is not only the basis for maintaining the morphology of cells but is also key to the transport of materials within cells (27).…”

“…TPX2 has been considered as an important regulator of human cancers or a promising therapeutic target for treatment, and overexpression of TPX2 is associated with the progress of human malignancies or the poor prognosis of human patients, especially those with PC (10,11). Recently, increasing data has indicated that TPX2 not only functions by way of modulating tubulin assembling, but could also promote the invasion of cancerous cells via some other mechanisms; TPX2 could enhance the metastasis of cancerous cells via an enhancement of the expression level of mmps (12,13). In the present study, our results revealed a novel mechanism of TPX2 in its ability to promote the invasion of PC-3 cells, a typical ARdeficiency PC cells, by interacting with ETS-1 and enhancing its transcription factor activation.…”

Identification of molecular markers associated with diagnosis and prognosis in lung adenocarcinoma by bioinformatics analysis

“…Except for these function, in various cancers can TPX2 also control bladder cancer cell's proliferation and invasion via TPX2-p53-GLIPR1 regulatory circuitry [41], regulate the PI3K/AKT signaling pathway to facilitate hepatocellular carcinoma [42], interactive with miRNA such as miR-485-3p [43], miR-361-5p [44], miR-335-5p [45], miR-216b [46] and so on. Zhou et al have veri ed that TPX2 can activate the epithelial-mesenchymal transition process and promote both the expression and activities of matrix metalloproteinase (MMP)2 and MMP9 in non-small cell lung cancer (NSCLC), which means TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC [47].…”

Identification of Molecular Markers Associated with Diagnosis and Prognosis in Lung Adenocarcinoma by Bioinformatics Analysis

“…Except for these function, in various cancers can TPX2 also control bladder cancer cell's proliferation and invasion via TPX2-p53-GLIPR1 regulatory circuitry [40], regulate the PI3K/AKT signaling pathway to facilitate hepatocellular carcinoma [41], interactive with miRNA such as miR-485-3p [42], miR-361-5p [43], miR-335-5p [44], miR-216b [45] and so on. Zhou et al have veri ed that TPX2 can activate the epithelial-mesenchymal transition process and promote both the expression and activities of matrix metalloproteinase (MMP)2 and MMP9 in non-small cell lung cancer (NSCLC), which means TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC [46]. Some studies have con rmed that COL1A1-related miRNAs were involved in the regulation of different kinds of tumors, including LUAD [17,47].…”