TY - JOUR
T1 - Transient SNAIL1 expression is necessary for metastatic competence in breast cancer
AU - Tran, Hung D.
AU - Luitel, Krishna
AU - Kim, Michael
AU - Zhang, Kun
AU - Longmore, Gregory D.
AU - Tran, David D.
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a genetic SNAIL1 model by coupling an endogenous SNAIL1 reporter with an inducible SNAIL1 transgene. Using multiple genetic models of breast cancer, we demonstrated that endogenous SNAIL1 expression was restricted to primary tumors that ultimately disseminate. SNAIL1 gene deletion either during the premalignant phase or after primary tumors have reached a palpable size blunted metastasis, indicating that late metastasis was the main driver of metastasis and that this was dependent on SNAIL1. Importantly, SNAIL1 expression during breast cancer metastasis was transient and forced transient, but not continuous. SNAIL1 expression in breast tumors was sufficient to increase metastasis.
AB - SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a genetic SNAIL1 model by coupling an endogenous SNAIL1 reporter with an inducible SNAIL1 transgene. Using multiple genetic models of breast cancer, we demonstrated that endogenous SNAIL1 expression was restricted to primary tumors that ultimately disseminate. SNAIL1 gene deletion either during the premalignant phase or after primary tumors have reached a palpable size blunted metastasis, indicating that late metastasis was the main driver of metastasis and that this was dependent on SNAIL1. Importantly, SNAIL1 expression during breast cancer metastasis was transient and forced transient, but not continuous. SNAIL1 expression in breast tumors was sufficient to increase metastasis.
UR - http://www.scopus.com/inward/record.url?scp=84909606776&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-14-0923
DO - 10.1158/0008-5472.CAN-14-0923
M3 - Article
C2 - 25164016
AN - SCOPUS:84909606776
SN - 0008-5472
VL - 74
SP - 6330
EP - 6340
JO - Cancer research
JF - Cancer research
IS - 21
ER -