Open AccessIdentification of a novel role of S eptin 10 in paclitaxel‐resistance in cancers through a functional genomics screen
Author(s) -
Xu Mingli,
Takanashi Masakatsu,
Oikawa Kosuke,
Nishi Hirotaka,
Isaka Keiichi,
Yoshimoto Takayuki,
Ohyashiki Junko,
Kuroda Masahiko
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02221.x
Subject(s) - paclitaxel , taxane , cancer research , biology , cancer , breast cancer , genetics
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 si RNA library against the entire human genomes to identify genes associated with sensitivity to paclitaxel. We isolated two paclitaxel‐resistant clones carrying the si RNA specific to septin 10 ( SEPT 10 ) 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 SEPT 10 remains unknown. Interestingly, overexpression of SEPT 10 increased cells’ sensitivity to paclitaxel; we also found that SEPT 10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel‐resistant tumors had decreased expression of SEPT 10. Thus, SEPT 10 may be a novel candidate molecule that acts as a good indicator of paclitaxel‐resistant carcinomas ( Cancer Sci 2012; 103: 821–827)