Astrin/SPAG5 is a mitotic spindle
protein found to be overexpressed in several human
cancers, functioning as an oncogene. The expression of
Astrin has not been reported so far in
colon cancer, nor has it been related to HIFs expression or action. Since mTOR,
Astrin, and
hypoxia-inducible factors (HIFs) are involved in promoting the growth and survival of
cancer cells, we investigated the possible interaction between them in cultured
colon cancer cells. Both
Astrin and HIF-1α and HIF-2α
protein levels were found only expressed in
colon cancer cells compared with nonmalignant cells. Our data indicate that mTOR stimulates both
Astrin and HIFs expression, but notably, mTORC activity seems to be independent of
Astrin expression levels. However, while HIF-1α or HIF-2α stable knockdown increased
Astrin expression, mTOR activity was affected in an opposite way by HIF-1α or HIF-2α silencing, indicating that HIF-1α inhibits mTOR while HIF-2α stimulates its activity. These data suggest that mTOR,
Astrin, and HIFs compose an integrative network interacting to activate positive or negative regulatory loops probably to coordinate
cancer cell growth, metabolism, and survival under oncogenic stress.