Gene interactions and pathways from curated databases and text-mining
Proc Natl Acad Sci U S A 2008, PMID: 18650380

ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo.

Schewe, Denis M; Aguirre-Ghiso, Julio A

The pathways that allow quiescent disseminated cancer cells to survive during prolonged dormancy periods are unknown. Here, we identify the transcription factor ATF6alpha as a pivotal survival factor for quiescent but not proliferative squamous carcinoma cells. ATF6alpha is essential for the adaptation of dormant cells to chemotherapy, nutritional stress, and, most importantly, the in vivo microenvironment. Mechanism analysis showed that MKK6 and p38alpha/beta contribute to regulating nuclear translocation and transcriptional activation of ATF6alpha in dormant cancer cells. Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt. Down-regulation of ATF6alpha or Rheb reverted dormant tumor cell resistance to rapamycin and induced pronounced killing only of dormant cancer cells in vivo. Knocking down ATF6alpha also prolonged the survival of nude mice bearing dormant tumor cells. Targeting survival signaling by the ATF6alpha-Rheb-mTOR pathway in dormant tumor cells may favor the eradication of residual disease during dormancy periods.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Squamous Cell, Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Rheb → mTOR signaling: " Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt "

Rheb → ATF6alpha: " Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt "

mTOR signaling → ATF6alpha: " Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt "

Manually curated Databases

No curated data.