Gain or loss of TGFbeta signaling in mammary carcinoma cells can promote metastasis.
The transforming growth factor beta (TGFbeta) is a potent regulator of tumor initiation, progression and metastasis. It has been known for many years that TGFbeta signaling in the carcinoma cell can suppress or promote tumor progression depending on the context of stimulation. While the impact of TGFbeta on the carcinoma cell is significant, it is now generally accepted that primary and metastatic carcinoma progression is regulated by an intricate network of host-tumor cell interactions. Interestingly, recent results have revealed that gain or loss of TGFbeta signaling in carcinoma cells can promote metastasis through carcinoma cell derived TGFbeta dependent host-tumor cell interactions in vivo. Further, gain or complete abrogation of TGFbeta signaling was shown to result in gene expression signatures that correlated with poor patient prognosis in breast cancer. Specifically, the TGFbeta responsive gene expression signature correlated with poor prognosis for estrogen receptor negative (ER(-)) breast cancer while complete abrogation of TGFbeta signaling resulted in a correlation with poor outcome in lymph node positive (LN(+)) and ER(+) breast cancers. Importantly, in both cases the correlation with poor prognosis was linked to carcinoma cell derived interactions with the adjacent microenvironment. Together the current results suggest that, in addition to intrinsic carcinoma cell signaling, TGFbeta dependent host-tumor cell interactions should be considered when designing therapeutic strategies to manage carcinoma progression.
Bierie
Brian
B
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Moses
Harold L
HL
D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D018925:Chemokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D018925:Chemokines; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta