Title

Tumor cell dependence on Ran-GTP-directed mitosis

PubMed ID

18339863

UMMS Affiliation

Department of Cancer Biology

Date

3-15-2008

Document Type

Article

Subjects

Animals; Cell Death; Cell Line, Tumor; HCT116 Cells; Hela Cells; Humans; Mice; Mitosis; Neoplasms; RNA, Small Interfering; Signal Transduction; ran GTP-Binding Protein

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Deregulated cell division is a hallmark of cancer, but whether tumor cells become dependent on specific mitotic mechanisms is not known. Here, we show that the small GTPase Ran, a regulator of mitotic spindle formation, is differentially overexpressed in human cancer as compared with normal tissues, in vivo. Acute silencing of Ran in various tumor cell types causes aberrant mitotic spindle formation, mitochondrial dysfunction, and apoptosis. This pathway does not require p53, Bax, or Smac, but is controlled by survivin as a novel Ran target in cancer. Conversely, loss of Ran in normal cells is well tolerated and does not result in mitotic defects or loss of cell viability. Therefore, tumor cells can become dependent on Ran signaling for cell division, and targeting this pathway may provide a novel and selective anticancer strategy.

Rights and Permissions

Citation: Cancer Res. 2008 Mar 15;68(6):1826-33. Link to article on publisher's site

Related Resources

Link to Article in PubMed