Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces.


BACKGROUND:Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity regulates the structure and cohesion of spindle poles. RESULTS:We inactivated Aurora-A in human U2OS osteosarcoma cells either by RNA-interference-mediated silencing or treating cultures with the specific inhibitor MLN8237. We show that mitotic spindle pole fragmentation induced by Aurora-A inactivation is associated with microtubule hyperstabilisation. Silencing of the microtubule-stabilising factor ch-TOG prevents spindle pole fragmentation caused by inactivation of Aurora-A alone and concomitantly reduces the hyperstabilisation of microtubules. Furthermore, decreasing pole-directed spindle forces by inhibition of the Eg5 kinesin, or by destabilisation of microtubule-kinetochore attachments, also prevents pole fragmentation in Aurora-A-inactivated mitoses. CONCLUSIONS:Our findings indicate that microtubule-generated forces are imbalanced in Aurora-A-defective cells and exert abnormal pressure at the level of spindle poles, ultimately causing their fragmentation. This study therefore highlights a novel role of the Aurora-A kinase in regulating the balance between microtubule forces during bipolar spindle assembly.


Mol Cancer


Molecular cancer


Asteriti IA,Giubettini M,Lavia P,Guarguaglini G




Has Abstract


2011-10-19 00:00:00










  • Growth factor receptor-Src-mediated suppression of GRK6 dysregulates CXCR4 signaling and promotes medulloblastoma migration.

    abstract:BACKGROUND:Metastasis in medulloblastoma (MB) is associated with poor survival. Recent genetic studies revealed MB to comprise distinct molecular subgroups, including the sonic hedgehog (SHH) subgroup that exhibits a relatively high rate of progression. To identify targeted therapeutics against metastasis, a better und...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Yuan L,Zhang H,Liu J,Rubin JB,Cho YJ,Shu HK,Schniederjan M,MacDonald TJ

    更新日期:2013-03-05 00:00:00

  • Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells.

    abstract:BACKGROUND:Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. RESULTS:Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Liu H,Ippolito GC,Wall JK,Niu T,Probst L,Lee BS,Pulford K,Banham AH,Stockwin L,Shaffer AL,Staudt LM,Das C,Dyer MJ,Tucker PW

    更新日期:2006-05-16 00:00:00

  • Liquid biomarkers in melanoma: detection and discovery.

    abstract::A vast array of tumor-derived genetic, proteomic and cellular components are constantly released into the circulation of cancer patients. These molecules including circulating tumor DNA and RNA, proteins, tumor and immune cells are emerging as convenient and accurate liquid biomarkers of cancer. Circulating cancer bio...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审


    authors: Lim SY,Lee JH,Diefenbach RJ,Kefford RF,Rizos H

    更新日期:2018-01-17 00:00:00

  • Thyroid cancers of follicular origin in a genomic light: in-depth overview of common and unique molecular marker candidates.

    abstract::In recent years, thyroid malignances have become more prevalent, especially among women. The most common sporadic types of thyroid tumors of follicular origin include papillary, follicular and anaplastic thyroid carcinomas. Although modern diagnosis methods enable the identification of tumors of small diameter, tumor ...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审


    authors: Pstrąg N,Ziemnicka K,Bluyssen H,Wesoły J

    更新日期:2018-08-08 00:00:00

  • Opposing roles for mammary epithelial-specific PPARγ signaling and activation during breast tumour progression.

    abstract:BACKGROUND:Among women worldwide, breast cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related deaths. Improved understanding of breast tumourigenesis may facilitate the development of more effective therapies. Peroxisome proliferator-activated receptor (PPAR)γ is a transcription ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Apostoli AJ,Roche JM,Schneider MM,SenGupta SK,Di Lena MA,Rubino RE,Peterson NT,Nicol CJ

    更新日期:2015-04-15 00:00:00

  • Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile.

    abstract:BACKGROUND:In high grade gliomas, 1p19q codeletion and EGFR amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with EGFR amplification, identified by CGH-array. RESULTS:The two...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Ducray F,Idbaih A,de Reyniès A,Bièche I,Thillet J,Mokhtari K,Lair S,Marie Y,Paris S,Vidaud M,Hoang-Xuan K,Delattre O,Delattre JY,Sanson M

    更新日期:2008-05-20 00:00:00

  • Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer.

    abstract:BACKGROUND:TGF-β promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-β-induced EMT and m...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Wang L,Tong X,Zhou Z,Wang S,Lei Z,Zhang T,Liu Z,Zeng Y,Li C,Zhao J,Su Z,Zhang C,Liu X,Xu G,Zhang HT

    更新日期:2018-09-27 00:00:00

  • Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions.

    abstract::Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of...

    journal_title:Molecular cancer

    pub_type: 杂志文章,收录出版,评审


    authors: Mehrotra R,Gupta A,Singh M,Ibrahim R

    更新日期:2006-03-23 00:00:00

  • Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.

    abstract:BACKGROUND:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood. Recent evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including HCC. Taurine Up-regulated Gene...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Huang MD,Chen WM,Qi FZ,Sun M,Xu TP,Ma P,Shu YQ

    更新日期:2015-09-04 00:00:00

  • RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy.

    abstract:BACKGROUND:The tetraspanin CD63 is a highly N-glycosylated protein that is known to regulate cancer malignancy. However, the contribution of glycosylation of CD63 to cancer malignancy remains unclear. Previously, we reported that ribophorin II (RPN2), which is part of an N-oligosaccharyle transferase complex, is respon...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Tominaga N,Hagiwara K,Kosaka N,Honma K,Nakagama H,Ochiya T

    更新日期:2014-05-31 00:00:00

  • Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression.

    abstract:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and local...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Chen Y,Wang D,Peng H,Chen X,Han X,Yu J,Wang W,Liang L,Liu Z,Zheng Y,Hu J,Yang L,Li J,Zhou H,Cui X,Li F

    更新日期:2019-01-04 00:00:00

  • Nano-based delivery of RNAi in cancer therapy.

    abstract:BACKGROUND:RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of ...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审


    authors: Xin Y,Huang M,Guo WW,Huang Q,Zhang LZ,Jiang G

    更新日期:2017-07-28 00:00:00

  • Na,K-ATPase β1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity.

    abstract:BACKGROUND:The Sonic hedgehog (Shh) signaling pathway plays an important role in cerebellar development, and mutations leading to hyperactive Shh signaling have been associated with certain forms of medulloblastoma, a common form of pediatric brain cancer. While the fundamentals of this pathway are known, the molecular...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Lee SJ,Litan A,Li Z,Graves B,Lindsey S,Barwe SP,Langhans SA

    更新日期:2015-08-19 00:00:00

  • The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines.

    abstract:BACKGROUND:The cyclin D1 proto-oncogene is an important regulator of G1 to S-phase transition and an important cofactor for several transcription factors in numerous cell types. Studies on neonatal cardiomyocytes and postmitotic neurons indicate that the activity of cyclin D1 may be regulated through its cytoplasmic se...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Alao JP,Gamble SC,Stavropoulou AV,Pomeranz KM,Lam EW,Coombes RC,Vigushin DM

    更新日期:2006-02-17 00:00:00

  • Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy.

    abstract:BACKGROUND:Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy affecting children. Despite significant progress and success in the treatment of ALL, a significant number of children continue to relapse and for them, outcome remains poor. Therefore, the search for novel therapeutic approaches ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Sengupta TK,Leclerc GM,Hsieh-Kinser TT,Leclerc GJ,Singh I,Barredo JC

    更新日期:2007-07-10 00:00:00

  • Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas.

    abstract:BACKGROUND:The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tu...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Console GM,Herenu CB,Camihort GA,Luna GC,Bracamonte MI,Morel GR,Goya RG

    更新日期:2008-01-25 00:00:00

  • Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells.

    abstract:BACKGROUND:The expression of the rodent phosphoinositide-specific phospholipase C delta-4 (PLCdelta4) has been found to be elevated upon mitogenic stimulation and expression analysis have linked the upregulation of PLCdelta4 expression with rapid proliferation in certain rat transformed cell lines. The human homologue ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Leung DW,Tompkins C,Brewer J,Ball A,Coon M,Morris V,Waggoner D,Singer JW

    更新日期:2004-05-13 00:00:00

  • LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells.

    abstract:BACKGROUND:Expression of kappa gene is under the control of distinct cis-regulatory elements, including the kappa intron enhancer (iE kappa) and the kappa 3' enhancer (3'E kappa). The active enhancers and expression of immunoglobulin is generally considered to be restricted to B lymphocytes. However, accumulating evide...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Liu H,Zheng H,Duan Z,Hu D,Li M,Liu S,Li Z,Deng X,Wang Z,Tang M,Shi Y,Yi W,Cao Y

    更新日期:2009-10-27 00:00:00

  • Oncogenic KRAS promotes malignant brain tumors in zebrafish.

    abstract:BACKGROUND:Zebrafish have been used as a vertebrate model to study human cancers such as melanoma, rhabdomyosarcoma, liver cancer, and leukemia as well as for high-throughput screening of small molecules of therapeutic value. However, they are just emerging as a model for human brain tumors, which are among the most de...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Ju B,Chen W,Orr BA,Spitsbergen JM,Jia S,Eden CJ,Henson HE,Taylor MR

    更新日期:2015-02-03 00:00:00

  • c-Jun NH2-terminal kinase-dependent upregulation of DR5 mediates cooperative induction of apoptosis by perifosine and TRAIL.

    abstract:BACKGROUND:Perifosine, an alkylphospholipid tested in phase II clinical trials, modulates the extrinsic apoptotic pathway and cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to augment apoptosis. The current study focuses on revealing the mechanisms by which perifosine enhances TRAIL-ind...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Fu L,Lin YD,Elrod HA,Yue P,Oh Y,Li B,Tao H,Chen GZ,Shin DM,Khuri FR,Sun SY

    更新日期:2010-12-20 00:00:00

  • Stromal ING1 expression induces a secretory phenotype and correlates with breast cancer patient survival.

    abstract:BACKGROUND:Previous studies have established that levels of the Inhibitor of Growth 1(ING1) tumor suppressor are reduced in a significant proportion of different cancer types. Here we analyzed levels of ING1 in breast cancer patients to determine its prognostic significance as a biomarker for breast cancer prognosis. ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Thakur S,Nabbi A,Klimowicz A,Riabowol K

    更新日期:2015-08-27 00:00:00

  • The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1.

    abstract:BACKGROUND:Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metab...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Zhao Y,Liu Y,Lin L,Huang Q,He W,Zhang S,Dong S,Wen Z,Rao J,Liao W,Shi M

    更新日期:2018-03-06 00:00:00

  • Efficient TGF-β/SMAD signaling in human melanoma cells associated with high c-SKI/SnoN expression.

    abstract:BACKGROUND:SKI and SnoN proteins have been shown to inhibit TGF-β signaling, acting both as transcriptional co-repressors in the cell nucleus, and as sequestrators of SMAD proteins in the cytoplasm. TGF-β, on the other hand, induces rapid, proteasome-mediated, degradation of both proteins. How elevated SKI and SnoN pro...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Javelaud D,van Kempen L,Alexaki VI,Le Scolan E,Luo K,Mauviel A

    更新日期:2011-01-06 00:00:00

  • Sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines.

    abstract:BACKGROUND:Hodgkin lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL), are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization to ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Fadlelmola FM,Zhou M,de Leeuw RJ,Dosanjh NS,Harmer K,Huntsman D,Lam WL,Banerjee D

    更新日期:2008-01-07 00:00:00

  • A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3.

    abstract:BACKGROUND:Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application o...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: He X,Chai P,Li F,Zhang L,Zhou C,Yuan X,Li Y,Yang J,Luo Y,Ge S,Zhang H,Jia R,Fan X

    更新日期:2020-07-15 00:00:00

  • Dovitinib synergizes with oxaliplatin in suppressing cell proliferation and inducing apoptosis in colorectal cancer cells regardless of RAS-RAF mutation status.

    abstract:BACKGROUND:Cancer is the result of a multistep process of genomic alterations, including mutations in key regulatory proteins that result in loss of balanced gene expression and subsequent malignant transformation. Throughout the various stages of colorectal carcinoma (CRC), complex genetic alterations occur, of which ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Gaur S,Chen L,Ann V,Lin WC,Wang Y,Chang VH,Hsu NY,Shia HS,Yen Y

    更新日期:2014-02-04 00:00:00

  • PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes.

    abstract:BACKGROUND:Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to dete...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Cristina C,Díaz-Torga GS,Goya RG,Kakar SS,Perez-Millán MI,Passos VQ,Giannella-Neto D,Bronstein MD,Becu-Villalobos D

    更新日期:2007-01-12 00:00:00

  • Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells.

    abstract:BACKGROUND:Colorectal cancers carrying the B-Raf V600E-mutation are associated with a poor prognosis. The purpose of this study was to identify B-RafV600E-mediated traits of cancer cells in a genetic in vitro model and to assess the selective sensitization of B-RafV600E-mutant cancer cells towards therapeutic agents. ...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Hirschi B,Gallmeier E,Ziesch A,Marschall M,Kolligs FT

    更新日期:2014-05-24 00:00:00

  • The ERalpha coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium.

    abstract::The HER4 intracellular domain (4ICD) is a potent estrogen receptor (ERalpha) coactivator with activities in breast cancer and the developing mammary gland that appear to overlap with progesterone receptor (PgR). In fact, 4ICD has recently emerged as an important regulator and predictor of tamoxifen response, a role pr...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Rokicki J,Das PM,Giltnane JM,Wansbury O,Rimm DL,Howard BA,Jones FE

    更新日期:2010-06-15 00:00:00

  • Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7/NFκB/c-Myc signaling in female esophageal carcinoma.

    abstract:BACKGROUND:Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol con...

    journal_title:Molecular cancer

    pub_type: 杂志文章


    authors: Li W,Zhang L,Guo B,Deng J,Wu S,Li F,Wang Y,Lu J,Zhou Y

    更新日期:2019-02-08 00:00:00