TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT

Zheng, Bingbing; Li, Jiaxi; Lv, Xin; Zhang, Han; Yu, Fajun; Kong, Ling-Dong; Li, Yimin; Yu, Mengqi; Lü, Fang; Liang, Bo

doi:10.1016/j.biopha.2018.08.011

Cited by 20 publications

(17 citation statements)

References 28 publications

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“…3A). Previous studies demonstrated that epithelial-to-mesenchymal transition (EMT) is a crucial process for cancer cell mobility (19)(20)(21). To determine whether miR-137 inhibits the mobility of HuccT1 and TFK-1 cells via affecting the EMT phenotype, western blotting was conducted to detect the protein levels of two key markers of EMT, N-cadherin and vimentin.…”

Section: Mir-137 Represses Cca Cell Migration and Invasion In Vitromentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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It is widely known that abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the occurrence or development of tumors. The objective of the present study was to elucidate the function and underlying mechanism of miR-137 in the progression of cholangiocarcinoma (ccA). The expression levels of miR-137 in ccA tissues and cell lines were measured using reverse transcription-quantitative PcR. The role of miR-137 in the proliferation of ccA cells was assessed using the cell counting Kit-8 assay, colony formation assay and cell cycle distribution analysis, while its effects on the migration and invasion of ccA cells were evaluated using Transwell assays. The function of miR-137 on ccA growth in vivo was also investigated using a xenograft mouse model. Furthermore, the association between miR-137 and Wnt family member 2B (WNT2B) was analyzed using bioinformatics, double luciferase assay and western blotting. It was verified that the expression of miR-137 was low in ccA tissues and cell lines, whereas increased expression of miR-137 significantly suppressed cell proliferation, decreased colony formation ability and induced G1 phase arrest. miR-137 overexpression suppressed the migration and invasion ability of TFK-1 and HuccT1 cells. Furthermore, the results of the xenograft mouse model assays revealed that miR-137 overexpression decreased tumor growth in vivo. The results of bioinformatics analysis and dual luciferase reporter assays demonstrated that WNT2B is directly regulated by miR-137. The expression of WNT2B and Wnt-pathway-related proteins was decreased when miR-137 was overexpressed. Restoring the expression of WNT2B notably reversed the inhibitory effect of miR-137 on CCA cells. Therefore, the findings of the present study demonstrated that miR-137 acts as a suppressor in ccA and inhibits ccA cell proliferation, migration and invasion through suppressing the expression of WNT2B.

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Section: Mir-137 Represses Cca Cell Migration and Invasion In Vitromentioning

confidence: 99%

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

et al. 2020

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“…TPX2 is a protein involved in spindle apparatus assembly and specifically associated to cell microtubules [38]. The TPX2 gene is part of the signature of chromosomal instability from specific genes whose expression was consistently correlated with clinical outcome in multiple human cancers [40,41], and it has been identified as a driving oncogene in different kinds of neoplasm [42,43,44,45,46,47]. To the best of our knowledge, GOLPH3 associated resistance to chemotherapy and its underlying mechanism in human NB have not been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy

Ognibene

Podestà

Garaventa

et al. 2019

IJMS

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Neuroblastoma (NB) is an aggressive, relapse-prone infancy tumor of the sympathetic nervous system and is the leading cause of death among preschool age diseases, so the search for novel therapeutic targets is crucial. Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development, and in the DNA damage response, of various human cancers. Golgi dispersal is a common feature of DNA damage response in mammalian cells. Understanding how cells react to DNA damage is essential in order to recognize the systems used to escape from elimination. We induced DNA damage in two human neuroblastoma cell lines by curcumin. The exposure of neuroblastoma cells to curcumin induced: (a) up-regulation of GOLPH3+ cells; (b) augmentation of double-strand breaks; (c) Golgi fragmentation and dispersal throughout the cytoplasm; (d) increase of apoptosis and autophagy; (e) increased expression of TPX2 oncoprotein, able to repair DNA damage. Primary neuroblastoma samples analysis confirmed these observations. Our findings suggest that GOLPH3 expression levels may represent a clinical marker of neuroblastoma patients’ responsiveness to DNA damaging therapies—and of possible resistance to them. Novel molecules able to interfere with GOLPH3 and TPX2 pathways may have therapeutic benefits when used in combination with standard DNA damaging therapeutic agents in neuroblastoma

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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The prognosis for endocrine-independent prostate carcinoma is still poor due to its highly metastatic feature. In the present work, TPX2 (the targeting protein for Xklp2), which is known as a micro-tubulin interacted protein, was identified as a novel coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies. TPX2 enhanced the transcription factor activation of ETS-1 and increased the expression of ETS-1’s downstream metastasis-related genes, such as mmp3 or mmp9, induced by HGF (hepatocyte growth factor), a typical agonist of the HGF/c-MET/ETS-1 pathway. The protein-interaction between TPX2 and ETS-1 was examined using immunoprecipitation (IP). TPX2 enhanced the accumulation of ETS-1 in the nuclear and the recruitment of its binding element (EST binding site, EBS) located in the promoter region of its downstream gene, mmp9. Moreover, TPX2 enhanced the in vitro or in vivo invasion of a typical endocrine-independent prostate carcinoma cell line, PC-3. Therefore, TPX2 enhanced the activation of the HGF/ETS-1 pathway to enhance the invasion of endocrine-independent prostate carcinoma cells and thus it would be a promising target for prostate carcinoma treatment.

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TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT

Cited by 20 publications

References 28 publications

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B

Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy

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

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