|Awarded On||February 16, 2022|
|Title||KRAS mutation-induced KDM5D upregulation promotes male-specific colorectal cancer metastasis|
|Award Mechanism||Individual Investigator|
|Institution/Organization||The University of Texas M.D. Anderson Cancer Center|
|Principal Investigator/Program Director||Ronald DePinho|
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US. Moreover, the metastasis and mortality rates are strikingly higher in men than in women. Intriguingly, these gender differences in CRC are observed only in tumors that have a KRAS mutated (KRAS*) gene. The molecular basis for these gender differences is not known.
In our mouse model of KRAS* CRC, these gender differences are also observed, providing a genetic model with which to study the mechanisms underlying how KRAS* may regulate higher metastasis and poorer survival in males. Our preliminary data have uncovered that KRAS* activates STAT4 which directly up-regulates the level of a Y chromosome-linked d...