This application is a renewal of an ongoing project to understand mitotic or cell division defects in cancer. Our goals are to identify the source of the defects and their impact on oncogenesis. Within this broad category, the project will focus on the source of centrosome amplification and polyploidy. This is a newly emerging area of cancer biology and the mechanisms are poorly understood. Both cancer and normal cells grown in culture will be investigated. We have shown that cancer cells often fail to divide properly because of defects in regulatory myosin light chain phosphorylation. We believe that this is due to inhibition of the kinase responsible for adding the phosphate to the myosin light chain. We propose to determine how this kinase is inhibited in tumor cells. If the mistakes in division are understood, we might be able to prevent the abnormal proliferation of cells in tumors.
Cancer is found in more than 1.4 million Americans each year and kills almost 600,000. This study examines the cellular defects that result in cancer cells having genetic instability that ultimately results in cancer spread and resistance to therapy. The results of this study may lead to new prognostic tests and better therapies for this deadly disease.
|Sankunny, Madhav; Parikh, Rahul A; Lewis, Dale W et al. (2014) Targeted inhibition of ATR or CHEK1 reverses radioresistance in oral squamous cell carcinoma cells with distal chromosome arm 11q loss. Genes Chromosomes Cancer 53:129-43|
|Bartoli, Kristen M; Jakovljevic, Jelena; Woolford Jr, John L et al. (2011) Kinesin molecular motor Eg5 functions during polypeptide synthesis. Mol Biol Cell 22:3420-30|
|Wu, Qian; Xu, Fengfeng L; Li, Youjun et al. (2010) The c-Myc target glycoprotein1balpha links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells. PLoS One 5:e10819|
|Wu, Q; Sahasrabudhe, R M; Luo, L Z et al. (2010) Deficiency in myosin light-chain phosphorylation causes cytokinesis failure and multipolarity in cancer cells. Oncogene 29:4183-93|
|Li, Youjun; Xu, Fengfeng L; Lu, Jie et al. (2010) Widespread genomic instability mediated by a pathway involving glycoprotein Ib alpha and Aurora B kinase. J Biol Chem 285:13183-92|
|Martin, Christa Lese; Reshmi, Shalini C; Ried, Thomas et al. (2008) Chromosomal imbalances in oral squamous cell carcinoma: examination of 31 cell lines and review of the literature. Oral Oncol 44:369-82|
|Acilan, Ceyda; Potter, Douglas M; Saunders, William S (2007) DNA repair pathways involved in anaphase bridge formation. Genes Chromosomes Cancer 46:522-31|
|Gollin, Susanne M (2007) Mechanisms leading to nonrandom, nonhomologous chromosomal translocations in leukemia. Semin Cancer Biol 17:74-9|
|Parikh, Rahul A; White, Jason S; Huang, Xin et al. (2007) Loss of distal 11q is associated with DNA repair deficiency and reduced sensitivity to ionizing radiation in head and neck squamous cell carcinoma. Genes Chromosomes Cancer 46:761-75|
|Quintyne, Nicholas J; Reing, Janet E; Hoffelder, Diane R et al. (2005) Spindle multipolarity is prevented by centrosomal clustering. Science 307:127-9|