| First Author | Schmid MC | Year | 2011 |
| Journal | Cancer Cell | Volume | 19 |
| Issue | 6 | Pages | 715-27 |
| PubMed ID | 21665146 | Mgi Jnum | J:173562 |
| Mgi Id | MGI:5014454 | Doi | 10.1016/j.ccr.2011.04.016 |
| Citation | Schmid MC, et al. (2011) Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly Activate Myeloid Cell PI3Kgamma, A Single Convergent Point Promoting Tumor Inflammation and Progression. Cancer Cell 19(6):715-27 |
| abstractText | Tumor inflammation promotes angiogenesis, immunosuppression, and tumor growth, but the mechanisms controlling inflammatory cell recruitment to tumors are not well understood. We found that a range of chemoattractants activating G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and Toll-like/IL-1 receptors (TLR/IL1Rs) unexpectedly initiate tumor inflammation by activating the PI3-kinase isoform p110gamma in Gr1+CD11b+ myeloid cells. Whereas GPCRs activate p110gamma in a Ras/p101-dependent manner, RTKs and TLR/IL1Rs directly activate p110gamma in a Ras/p87-dependent manner. Once activated, p110gamma promotes inside-out activation of a single integrin, alpha4beta1, causing myeloid cell invasion into tumors. Pharmacological or genetic blockade of p110gamma suppressed inflammation, growth, and metastasis of implanted and spontaneous tumors, revealing an important therapeutic target in oncology. |
