Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Neumayer, Gernot; Helfricht, Angela; Shim, Su Yeon; Le, Hoa; Lundin, Cecilia; Belzil, Camille; Chansard, Mathieu; Yu, Yaping; Lees‐Miller, Susan P.; Gruß, Oliver J.; Attikum, Haico van; Helleday, Thomas; Nguyen, Minh Dang

doi:10.1074/jbc.m112.385674

Cited by 37 publications

(55 citation statements)

References 85 publications

(87 reference statements)

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“…79,80 Upon ionizing radiation, TPX2 accumulates at DNA double strand breaks and associates with 2 regulators of the DNA damage response, MDC1 and ATM. 81 Overexpression of TPX2 results in decreased ionizing radiation-dependent γ-H2AX levels, whereas the opposite phenotype is observed upon TPX2 knockdown by RNA interference. This function is not associated with the mitotic roles of TPX2, since it is also observed in postmitotic neurons.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…This function is not associated with the mitotic roles of TPX2, since it is also observed in postmitotic neurons. 81 Whether Aurora-A is involved in this phenotype remains unknown. These data suggest that deregulation of TPX2 may be involved not only in chromosomal instability but also in genomic instability mediated by abnormal DNA damage response (Fig.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

Castro

Malumbres

2012

Genes & Cancer

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Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells.

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Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

Castro

Malumbres

2012

Genes & Cancer

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“…TPX2 has been recently reported to promote interkinetic nuclear migration in mouse neural cells, by re-organising apical microtubules during the G2 phase (Kosodo et al, 2011). DNA damage response (DDR): recent data show that TPX2 is involved in DDR to ionising radiations, by modulating the levels of γ-H2AX; TPX2 localises to DNA double strand breaks and interacts with DDR factors such as MDC1 (Neumayer et al, 2012). Previous data suggested a link between TPX2 and DDR: i) TPX2 is a putative substrate of the ATM/ATR kinases, as revealed in a large-scale proteomic screening (Matsuoka et al, 2007); ii) a functional interplay has been shown between Xenopus TPX2, the Aurora-A kinase and the p53 oncosuppressor (Pascreau et al, 2009).…”

Section: Functionmentioning

confidence: 99%

TPX2 (TPX2, microtubule-associated, homolog (Xenopus laevis))

Asteriti¹,

Guarguaglini²

2013

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…It has been found to be a nuclear proliferation-related protein which is implicated in the regulation of the cell mitosis. TPX2 is released in the early stage of mitosis; and plays a critical role in mitotic spindle formation and subsequent segregation of chromosomes at cell division [14] . In recent years, a connection between TPX2 and initiation, progression and prognosis of malignant tumor is becoming a focus of researches [15] .…”

Section: Introductionmentioning

confidence: 99%

“…Aberrant expression of TPX2 leads to improper spindle assembly and chromosomal instability; and these processes might be partly responsible for carcinogenesis [14] . However, the precise role of TPX2 in cancer progression is still not fully understood.…”

mentioning

confidence: 99%

Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker "LGR5" and the Proliferation Biomarker "TPX2" in Colorectal Carcinoma

Harb¹,

Hegazy²,

Gertallah³

et al. 2016

Journal of Tumor

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cantly positively correlated with location of the tumor, grade, stage, local recurrence, lymph node and distant metastasis (P <0.001). The expression of TPX2 in CRC was also found to be signifi cantly correlated with the previous parameters (P < 0.001). Both biomarkers were up-regulated in CRC than in the adjacent non tumorous tissues. High LGR5 and TPX2 immunohistochemical expressions were strongly correlated with worse 3-year overall survival (OS), local recurrence free survival (LRFS) and distant metastases free survival (DMFS) (P < 0.001). CONCLUSIONS: High immunohistochemical expressions of bothLGR5 and TPX2 and the positive correlation between both of them represent signs of poor prognosis of CRC. Mechanisms responsible for the initiation, progression, prognosis and adequate management of CRC have been studied [3] . Two theories of CRC carcinogenesis have been stated; a stochastic model, where any cell has the ability of cancer initiation, promotion and progression and a cancer stem cell (CSC) model, that only produced by transformed CSCs having the ability to self-renewal, abnormally differentiate and form a cancer [4] . Although, CSCs have been incriminated in colon carcinogenesis for several years, the complexity of their detection and isolation is still not precisely In order to detect and remove colon CSCs, a selective biomarker "LGR5 (leucine-rich-repeat-containing G-protein-coupled receptor 5)" might be required. At the same time, an abnormal expression of TPX2 (targeting protein for xenopus kinesin-like protein 2) has been found to be related to the development and progression of tumors. We aimed to evaluate the immunohistochemical expressions of LGR5 and TPX2 in CRC in a trial to clarify their relations to proliferation and metastasis of CRC, and hence its prognosis. MATERIALS AND METHODS: Immunohistochemical staining of both LGR5 and TPX2 was assessed in sections from sixty paraffin blocks of CRC. The relationships between their levels of expressions with the clinicopathological parameters and patient outcome were statistically analyzed. RESULTS:The immunoexpression of LGR5 in CRC was signifi-

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Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Cited by 37 publications

References 85 publications

Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

TPX2 (TPX2, microtubule-associated, homolog (Xenopus laevis))

Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker "LGR5" and the Proliferation Biomarker "TPX2" in Colorectal Carcinoma

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Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Cited by 37 publications

References 85 publications

Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

TPX2 (TPX2, microtubule-associated, homolog (Xenopus laevis))

Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker &quot;LGR5&quot; and the Proliferation Biomarker &quot;TPX2&quot; in Colorectal Carcinoma

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Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker "LGR5" and the Proliferation Biomarker "TPX2" in Colorectal Carcinoma