Small interfering RNA-induced CHFR silencing sensitizes oral squamous cell cancer cells to microtubule inhibitors.

Abstract:

:Alterations in the function of cell cycle checkpoints are frequently detected in oral squamous cell carcinomas (OSCCs), and are often associated with the sensitivity of the cancer cells to chemotherapeutic drugs. Recently, a mitotic checkpoint gene, Chfr, was shown to be inactivated by promoter methylation and point mutations in various human tumors. Here we show that the absence of its product, CHFR, is associated with mitotic checkpoint dysfunction, and that cancer cells lacking CHFR are sensitive to microtubule inhibitors. Checkpoint impairment appears to be caused by a prophase defect in this case, as OSCC cells lacking CHFR showed phosphorylation of histone H3 on Ser10 and translocation of cyclin B1 to the nucleus. When CHFR-deficient OSCC cells were treated with a microtubule inhibitor (docetaxel or paclitaxel), significant numbers of apoptotic cells were observed. Moreover, disruption of CHFR using small interfering RNA (siRNA) impaired the mitotic checkpoint, thereby reducing the ability of OSCC cells to arrest at G2/M phase and making them more sensitive to microtubule inhibitors. Our results suggest that CHFR could be a useful molecular target for chemotherapy.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Ogi K,Toyota M,Mita H,Satoh A,Kashima L,Sasaki Y,Suzuki H,Akino K,Nishikawa N,Noguchi M,Shinomura Y,Imai K,Hiratsuka H,Tokino T

doi

10.4161/cbt.4.7.1896

keywords:

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

773-80

issue

7

eissn

1538-4047

issn

1555-8576

pii

1896

journal_volume

4

pub_type

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