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

Zhou, Qinghong; Liu, Mingsheng; Shao, Tao; Xie, Pingbo; Zhu, Shaojie; Wang, Wei; Miao, Qiong; Peng, Jiaxi; Zhang, Peng

doi:10.3389/fonc.2021.618540

Cited by 7 publications

(7 citation statements)

References 46 publications

(56 reference statements)

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“…Several studies have found that a reduction in TPX2 levels is beneficial for cancer treatment. For example, the depletion of TPX2 can significantly inhibit prostate cancer and cholangiocarcinoma cell activity and migration, and TPX2 knockdown can inhibit tumor growth considerably in vivo [33][34][35]. Furthermore, the upregulation of TPX2 expression has been shown to significantly promote non-small-cell lung cancer, hepatocellular cell migration, and invasion; it has also been associated with increased cell plasticity [36,37].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Oncogenic Role of Targeting Protein for Xklp2 (TPX2) in Human Malignancies

et al. 2022

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Mitosis and spindle assembly require the microtubule-associated protein Xenopus kinesin-like protein 2 (TPX2). Although TPX2 is highly expressed in several malignant tumor forms, little is known about its role in cancer. In this study, we performed the gene set enrichment analysis of TPX2 in 33 types of cancers and an extensive pan-cancer bioinformatic analysis using prognosis, tumor mutational burdens, microsatellite instability, tumor microenvironment, and immune cell infiltration data. According to the differential expression study, TPX2 was found to be overexpressed across all studied cancer types. Based on the survival analysis, increased TPX2 expression was associated with a poor prognosis for most cancers. The TPX2 expression level was confirmed to correlate with the clinical stage, microsatellite instability, and tumor mutational burden across all cancer types. Furthermore, TPX2 expression has been linked to tumor microenvironments and immune cell infiltration, particularly in bladder urothelial carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Finally, the gene set enrichment analysis implicated TPX2 in the regulation of aminoacyl tRNA biosynthesis, which is the most important tumor cell cycle signaling pathway. This comprehensive pan-cancer analysis shows that TPX2 is a prognostic molecular biomarker for most cancers and suggests its potential as an effective therapeutic target for the treatment of these diseases.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Oncogenic Role of Targeting Protein for Xklp2 (TPX2) in Human Malignancies

et al. 2022

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“…Based on the factors that ETS-1 is not only an important regulator of human cancerous cells’ proliferation, but also enhancing the invasive ability of cells, the transwell assays were performed ( 16 , 18 , 71 ). The results were shown as the images of the invaded cells or the quantitative results of the images.…”

Section: Discussionmentioning

confidence: 99%

“…The transcription factor ETS-1 (E26 transformation-specific sequence 1) is an important regulator of malignant tumor cell proliferation that also has central roles in metastasis and invasion (16)(17)(18). Some evidence indicates that ETS-1 is closely related to the progression of a variety of tumors, including breast cancer and liver cancer, and its high expression is positively correlated with the degree of tumor malignancy (19,20).…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

et al. 2021

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The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

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“…It has previously been considered a micro-tubulin interacting protein and recently has been considered an important regulator of human malignancy proliferation and metastasis [ 7 , 8 ]. Our previous publication and some other publications reported that TPX2 may also function as regulators of transcription factors (ETS-1) or nuclear receptors (androgen receptor [AR]) [ 9 , 10 ]. However, the detailed role of TPX in HCC and specifically in HCC cellular resistance to antitumor drugs is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs

et al. 2023

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The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR’s downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein–protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4’s promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.

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

Cited by 7 publications

References 46 publications

Comprehensive Analysis of the Oncogenic Role of Targeting Protein for Xklp2 (TPX2) in Human Malignancies

Comprehensive Analysis of the Oncogenic Role of Targeting Protein for Xklp2 (TPX2) in Human Malignancies

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs

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