| First Author | Chiacchiera F | Year | 2012 |
| Journal | Cancer Lett | Volume | 324 |
| Issue | 1 | Pages | 98-108 |
| PubMed ID | 22579651 | Mgi Jnum | J:189311 |
| Mgi Id | MGI:5445038 | Doi | 10.1016/j.canlet.2012.05.006 |
| Citation | Chiacchiera F, et al. (2012) Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models. Cancer Lett 324(1):98-108 |
| abstractText | We recently demonstrated that p38alpha is required to maintain colorectal cancer (CRC) metabolism, as its inhibition leads to FoxO3A activation, autophagy, cell death, and tumor growth reduction both in vitro and in vivo. Here we show that inhibition of p38alpha is followed by TRAIL-mediated activation of caspase-8 and FoxO3A-dependent HER3 upregulation with consequent overactivation of the MEK-ERK1/2 survival pathway. p38alpha and MEK combined inhibition specifically induces apoptosis by enabling TRAIL signaling propagation through t-Bid and caspase-3, and fosters cell death in CRC cells and preclinical mouse models. Current MEK1-directed pharmacological strategies could thus be exploited, in combination with p38alpha inhibition, to develop new approaches for CRC treatment. |
