Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen.
Paclitaxel (also known as taxol) is a member of the taxane class of anticancer agents, which has a well-known mechanism that blocks cell mitosis and kills tumor cells, that is often used in clinics to treat cancer. However, some carcinomas such as breast, ovarian and non-small-cell lung cancers are often resistant to paclitaxel treatment. In this study, we used a lentiviral siRNA library against the entire human genomes to identify genes associated with sensitivity to paclitaxel. We isolated two paclitaxel-resistant clones carrying the siRNA specific to septin 10 (SEPT10) and to budding uninhibited by benzimidazoles 3. The relation of budding uninhibited by benzimidazoles 3 to paclitaxel sensitivity has already been established, but that of SEPT10 remains unknown. Interestingly, overexpression of SEPT10 increased cells' sensitivity to paclitaxel; we also found that SEPT10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel-resistant tumors had decreased expression of SEPT10. Thus, SEPT10 may be a novel candidate molecule that acts as a good indicator of paclitaxel-resistant carcinomas.
Departments of Molecular Pathology, Tokyo Medical University, Tokyo, USA.
Mingli
M
Xu
Masakatsu
M
Takanashi
Kosuke
K
Oikawa
Hirotaka
H
Nishi
Keiichi
K
Isaka
Takayuki
T
Yoshimoto
Junko
J
Ohyashiki
Masahiko
M
Kuroda
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008870:Microtubules / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use*; D000075223:Poly-ADP-Ribose Binding Proteins; D058112:Septins / Q000235:genetics / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; C489444:BUB3 protein, human; D001562:Benzimidazoles; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D053148:Caspase 3; C474375:SEPTIN10 protein, human; D058112:Septins; D017239:Paclitaxel