TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT

Liang, Bo; Jia, Chunhong; Huang, Yu; He, Hua; Li, Jialu; Liao, Hui; Liu, Xiao; Liu, Xincheng; Bai, Xiaochun; Yang, Dian

doi:10.1007/s10620-015-3730-9

Cited by 58 publications

(63 citation statements)

References 30 publications

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“…For instance, TPX2 -siRNA decreased the viability and proliferation capacity of colon, cervical, and hepatic cancer cell lines [13, 14, 18]. Similarly, TPX2 -siRNA induced cell apoptosis in hepatic cancer cell lines [12]. Moreover, injection of TPX2 -siRNA significantly reduced the growth and weight of already developed xenograft tumors in nude mice [13–15, 21, 22].…”

Section: Discussionmentioning

confidence: 99%

TPX2 expression is associated with poor survival in gastric cancer

et al. 2017

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BackgroundTargeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis.MethodsTumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues.ResultsThe mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013).ConclusionsOur results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

TPX2 expression is associated with poor survival in gastric cancer

et al. 2017

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“…Based on histological differences, liver cancer can be divided into three types, the most common of which is hepatocellular carcinoma (HCC), which accounts for approximately 90% of primary liver cancers [2, 3]. At present, experts believe that in China hepatitis B is one of the main pathogenic factors in HCC, and our previous work indicated that more than 90% of HCC patients are diagnosed with hepatitis B [4, 5], which can progress to liver fibrosis and cirrhosis, and may ultimately lead to tumorigenesis [6, 7]. Generally, HCC is initially asymptomatic and patients show typical symptoms only once the disease has progressed to the advanced stage.…”

Section: Introductionmentioning

confidence: 99%

“…However, our previous follow-up studies showed that recurrence or metastasis within five years is observed in approximately 60% of HCC patients undergoing radical resection [4, 5]. Most researchers think this phenomenon is correlated with biological characteristics of high recurrence and the metastatic potential of HCC [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in hepatocellular carcinoma

Liu

Xiang

et al. 2017

Oncotarget

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Ubiquitin-like with plant homeodomain and ring finger domains, 1 (UHRF1) is overexpressed in a variety of tumor tissues and is negatively correlated with prognosis of patients with cancers, yet so far, a comprehensive study of UHRF1 in hepatocellular carcinoma (HCC) has not been conducted. The present study was designed to explore the expression of UHRF1, associated clinical implications, and its possible functions in HCC. Reverse transcription-polymerase chain reaction and immunohistochemical staining were used to detect UHRF1 expression in HCC specimens including cancerous and noncancerous tissues. Associations of UHRF1 expression with demographic and clinicopathologic features in HCC were analyzed, and the effects of RNA interference of UHRF1 on cell proliferation, cell cycle, apoptosis, and migration were investigated in vitro and in vivo. UHRF1 mRNA and protein expression were both upregulated and negatively correlated with prognosis in HCC patients. Furthermore, inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression were observed in vitro and in vivo after UHRF1 knockdown, moreover, G2/M arrest was detected in HCC cells. In conclusion, elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in HCC.

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“…Several studies have demonstrated that TPX2 is overexpressed in different types of human cancers, including medullary thyroid cancer 13, esophageal squamous cell carcinoma (ESCC) 14, estrogen receptor-positive metastatic breast cancers 15 and bladder carcinoma 16, and promotes tumor growth and metastasis, including in HCC. The expression level of TPX2 was obviously higher in HCC, and TPX2 overexpression was positively correlated with poor prognosis, metastasis, recurrence and time of recurrence after curative resection 17-19. TPX2 might be beneficial for T-cell specific HCC immunotherapy 20.…”

Section: Introductionmentioning

confidence: 97%

Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability

Hsu¹,

Chen²,

Su³

et al. 2017

J. Cancer

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Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy. Therefore, we consider the targeting TPX2 could provide novel therapeutic strategies for cancer. In this study, increased TPX2 protein expression was present in 16 (42%) of 38 primary HCCs and was associated with advanced stage, distant metastatic HCCs and poor prognosis. Knockdown of TPX2 inhibited cancer cell growth and downregulation of cyclin A, cyclin E and CDK2 proteins. However, over-expressed EGFP-TPX2 protein enhanced the in vitro tumor spheroid formation and rescued the TPX2 depleted cell growth. Targeting TPX2 caused a rising impaired chromosomal instability resulting in multinuclearity, cell cycle progression arrest, apotosis, senescence and an increased polyploidy in cells. An image-cytometry analysis revealed cell cycle progression arrest after TPX2 inhibition. A correlation was observed between the downregulation of the protein levels of genes related to chromosomal segregation and spindle assembly checkpoint (securin, seprase, Aurora A, Aurora B, Cyclin B1, Cyclin B2, MPS1, BUB1, BUB3, MAD1 and MAD2) and increased cell ploidy, indicating mitotic progression failure and the loss of the balance of genomic instability. In vitro tumor spheroid assay and in vivo xenografts mouse model showed a therapeutic opportunity. Our findings indicate that targeting TPX2 lead to suppress tumorigenicity in liver cancer cells, suggesting that TPX2 is a potential target for anticancer therapy in HCC.

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TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT

Abstract: TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients.

Cited by 58 publications

References 30 publications

TPX2 expression is associated with poor survival in gastric cancer

TPX2 expression is associated with poor survival in gastric cancer

Elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in hepatocellular carcinoma

Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability

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