Decreased DC‑SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis

AbstractHepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to metastasis. Paraspeckle component 1 (PSPC1) upregulation has been identified as an HCC pro-metastatic activator associated with poor patient prognosis, but with a lack of targeting strategy. Here, we report that PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of β-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/β-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/β-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/β-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy.

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Dyskerin Overexpression in Human Hepatocellular Carcinoma Is Associated with Advanced Clinical Stage and Poor Patient Prognosis

PLoS ONE ◽

10.1371/journal.pone.0043147 ◽

2012 ◽

Vol 7 (8) ◽

pp. e43147 ◽

Cited By ~ 26

Author(s):

Bei Liu ◽

Jinglei Zhang ◽

Chen Huang ◽

Hui Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Stage ◽

Human Hepatocellular Carcinoma ◽

Advanced Clinical Stage ◽

Poor Patient ◽

Patient Prognosis

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Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma

Experimental Biology and Medicine ◽

10.1177/15353702211008380 ◽

2021 ◽

pp. 153537022110083

Author(s):

Yiting Qiao ◽

Yunxin Pei ◽

Miao Luo ◽

Muthukumar Rajasekaran ◽

Kam M Hui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Frequency ◽

Genetic Instability ◽

Dna Ploidy ◽

Human Hepatocellular Carcinoma ◽

Signaling Networks ◽

Preclinical Studies ◽

Dna Ploidy Pattern ◽

Ploidy Pattern ◽

Patient Prognosis

Cytokinesis, the final step of mitosis, is critical for maintaining the ploidy level of cells. Cytokinesis is a complex, highly regulated process and its failure can lead to genetic instability and apoptosis, contributing to the development of cancer. Human hepatocellular carcinoma is often accompanied by a high frequency of aneuploidy and the DNA ploidy pattern observed in human hepatocellular carcinoma results mostly from impairments in cytokinesis. Many key regulators of cytokinesis are abnormally expressed in human hepatocellular carcinoma, and their expression levels are often correlated with patient prognosis. Moreover, preclinical studies have demonstrated that the inhibition of key cytokinesis regulators can suppress the growth of human hepatocellular carcinoma. Here, we provide an overview of the current understanding of the signaling networks regulating cytokinesis, the key cytokinesis regulators involved in the initiation and development of human hepatocellular carcinoma, and their applications as potential diagnostic and therapeutic biomarkers.

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Differential gene expression in peritumoral brain zone of glioblastoma: role of SERPINA3 in promoting invasion, stemness and radioresistance of glioma cells and association with poor patient prognosis and recurrence

Journal of Neuro-Oncology ◽

10.1007/s11060-020-03685-4 ◽

2021 ◽

Author(s):

Vidya P. Nimbalkar ◽

Banavathy S. Kruthika ◽

Palavalasa Sravya ◽

Shilpa Rao ◽

Harsha S. Sugur ◽

...

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Glioma Cells ◽

Poor Patient ◽

Differential Gene ◽

Patient Prognosis

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PPM1D Is a Therapeutic Target in Childhood Neural Tumors

Cancers ◽

10.3390/cancers13236042 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6042

Author(s):

Jelena Milosevic ◽

Diana Treis ◽

Susanne Fransson ◽

Gabriel Gallo-Oller ◽

Baldur Sveinbjörnsson ◽

...

Keyword(s):

Cell Cycle Control ◽

Neuroblastoma Cells ◽

Negative Regulator ◽

Activating Mutations ◽

Poor Patient ◽

Chromosome 17Q ◽

Childhood Medulloblastoma ◽

Aggressive Tumors ◽

Patient Prognosis ◽

Mdm2 Inhibitor

Childhood medulloblastoma and high-risk neuroblastoma frequently present with segmental gain of chromosome 17q corresponding to aggressive tumors and poor patient prognosis. Located within the 17q-gained chromosomal segments is PPM1D at chromosome 17q23.2. PPM1D encodes a serine/threonine phosphatase, WIP1, that is a negative regulator of p53 activity as well as key proteins involved in cell cycle control, DNA repair and apoptosis. Here, we show that the level of PPM1D expression correlates with chromosome 17q gain in medulloblastoma and neuroblastoma cells, and both medulloblastoma and neuroblastoma cells are highly dependent on PPM1D expression for survival. Comparison of different inhibitors of WIP1 showed that SL-176 was the most potent compound inhibiting medulloblastoma and neuroblastoma growth and had similar or more potent effects on cell survival than the MDM2 inhibitor Nutlin-3 or the p53 activator RITA. SL-176 monotherapy significantly suppressed the growth of established medulloblastoma and neuroblastoma xenografts in nude mice. These results suggest that the development of clinically applicable compounds inhibiting the activity of WIP1 is of importance since PPM1D activating mutations, genetic gain or amplifications and/or overexpression of WIP1 are frequently detected in several different cancers.

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