MCT-1 oncogene downregulates p53 and destabilizes genome structure in the response to DNA double-strand damage

Hsu, Hsin-Ling; Choy, Chik On; Kasiappan, Ravi; Shih, Hung-Ju; Sawyer, Jeffrey R.; Shu, Chung-Li; Chu, Kang-Lin; Chen, Yi Rong; Hsu, Hsin-Fen; Gartenhaus, Ronald B.

doi:10.1016/j.dnarep.2007.02.028

Cited by 30 publications

(43 citation statements)

References 58 publications

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“…Non-tumorigenic human breast epithelial MCF-10A cells were transduced with pLXSN vehicle or V5-tagged MCT-1 (pLXSN-MCT-1-V5). 37 The master cultures of vector control and MCT-1-expressing cells were studied. To further inactivate the p53 gene, cells were subsequently transfected with pMKO.1 puro or pMKO.1 puro p53 shRNA 2 (Addgene) using the jetPEI transfection reagent (Polyplus-transfection).…”

Section: Methodsmentioning

confidence: 99%

“…34,35 MCT-1 functions importantly in translation initiation in eukaryotes, 36 which may be related to MCT-1's documented oncogenic impacts on perturbation of kinase signal transduction, DNA damage response and translation regulation. [37][38][39][40] In supporting MCT-1's tumorigenic role, overexpression of MCT-1 transforms normal breast epithelial cells and downregulates p53 expression at both gene and protein levels. 35,37,41 Moreover, MCT-1 oncogene promotes chromosome abnormalities in the p53-compromised cells upon genotoxic damage and enhances the xenograft tumorigenicity of H1299 (p53-null) lung cancer cells.…”

Section: The Involvement Of Mct-1 Oncoprotein In Inducing Mitotic Catmentioning

confidence: 99%

“…[37][38][39][40] In supporting MCT-1's tumorigenic role, overexpression of MCT-1 transforms normal breast epithelial cells and downregulates p53 expression at both gene and protein levels. 35,37,41 Moreover, MCT-1 oncogene promotes chromosome abnormalities in the p53-compromised cells upon genotoxic damage and enhances the xenograft tumorigenicity of H1299 (p53-null) lung cancer cells. 35 Though MCT-1 is phosphorylated by CDC2 and ERK kinase in vitro, 42 it is unknown whether MCT-1 is implicated in mitotic function.…”

Section: The Involvement Of Mct-1 Oncoprotein In Inducing Mitotic Catmentioning

confidence: 99%

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The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

Shih

Chu

et al. 2012

Cell Cycle

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Section: Methodsmentioning

confidence: 99%

Section: The Involvement Of Mct-1 Oncoprotein In Inducing Mitotic Catmentioning

confidence: 99%

Section: The Involvement Of Mct-1 Oncoprotein In Inducing Mitotic Catmentioning

confidence: 99%

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The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

Shih

Chu

et al. 2012

Cell Cycle

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“…The resistances to apoptosis and deregulation of DNA damage checkpoints have been identified in the oncoprotein MCT-1 (multiple copies in a T-cell malignancy)-expressing cells (21)(22)(23). MCT-1 gene amplification was firstly recognized in the human B-cell and T-cell lymphoma (21).…”

Section: Introductionmentioning

confidence: 99%

“…MCT-1 gene amplification was firstly recognized in the human B-cell and T-cell lymphoma (21). Ectopic expression of MCT-1 accelerates p53 protein degradation by activation of the AKT-MDM2-proteosome pathway (23). Genome abnormalities, including chromosome amplification and translocation, are accumulated as MCT-1 reduces p53 activity.…”

Section: Introductionmentioning

confidence: 99%

Loss of p53 and MCT-1 Overexpression Synergistically Promote Chromosome Instability and Tumorigenicity

Kasiappan

Shih

Chu

et al. 2009

Molecular Cancer Research

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MCT-1 oncoprotein accelerates p53 degradation by means of the ubiquitin-dependent proteolysis. Our present data show that induction of MCT-1 increases chromosomal translocations and deregulated G 2 -M checkpoint in response to chemotherapeutic genotoxin. Remarkably, increases in chromosome copy number, multinucleation, and cytokinesis failure are also promoted while MCT-1 is induced in p53-deficient cells. In such a circumstance, the Ras-mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase signaling activity and the expression of metastatic molecules are amplified. Given a p53-silencing background, MCT-1 malignantly transforms normal breast epithelial cells that are satisfactory for stimulating cell migration/ adhesion and tumorigenesis. Detailed analyses of MCT-1 oncogenicity in H1299 p53-null lung cancer cells have shown that ectopically expressed MCT-1 advances xenograft tumorigenicity and angiogenesis, which cannot be completely suppressed by induction of p53. MCT-1 counteracts mutually with p53 at transcriptional levels. Clinical validations confirm that MCT-1 mRNA levels are differentially enriched in comparison between human lung cancer and nontumorigenic tissues. The levels of p53 mRNA are comparatively reduced in a subset of cancer specimens, which highly present MCT-1 mRNA. Our results indicate that synergistic promotions of chromosomal imbalances and oncogenic potency as a result of MCT-1 expression and p53 loss play important roles in tumor development.

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Anti‐tumor effects of miR‐34a by regulating immune cells in the tumor microenvironment

2023

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Malignant tumors pose a serious threat to human health. The development of malignant tumors is characterized by uncontrolled cell division and immune evasion. The micro‐ribonucleic acid‐34a (miR‐34a) is a small noncoding single‐stranded ribonucleic acid that is ubiquitously present in normal human tissues. However, it has been confirmed to be dysregulated in a variety of tumor cells. Numerous research have revealed the importance of miR‐34a in the treatment of various malignancies. MiR‐34a deletion can hasten the growth of tumors whereas miR‐34a overexpression suppresses the proliferation, invasion, and migration of cancer cells. Moreover, more recent studies have highlighted its role in immunity and investigated its applicability to particular tumors. Through various immune cells, factors, and other mechanisms, miR‐34a can inhibit tumor carcinogenesis. In view of the important role of miR‐34a in tumors, this research reviewed the aspects of miR‐34a regulation of tumor immune microenvironment to exert anti‐tumor effects in order to clarify the potential immunotherapy value of miR‐34a in tumors.

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MCT-1 oncogene downregulates p53 and destabilizes genome structure in the response to DNA double-strand damage

Cited by 30 publications

References 58 publications

The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

Loss of p53 and MCT-1 Overexpression Synergistically Promote Chromosome Instability and Tumorigenicity

Anti‐tumor effects of miR‐34a by regulating immune cells in the tumor microenvironment

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