| First Author | Zhuang X | Year | 2017 |
| Journal | Nat Cell Biol | Volume | 19 |
| Issue | 10 | Pages | 1274-1285 |
| PubMed ID | 28892080 | Mgi Jnum | J:246436 |
| Mgi Id | MGI:5920575 | Doi | 10.1038/ncb3613 |
| Citation | Zhuang X, et al. (2017) Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1. Nat Cell Biol 19(10):1274-1285 |
| abstractText | Metastatic cancer is a systemic disease, and metastasis determinants might elicit completely different effects in various target organs. Here we show that tumour-secreted DKK1 is a serological marker of breast cancer metastasis organotropism and inhibits lung metastasis. DKK1 suppresses PTGS2-induced macrophage and neutrophil recruitment in lung metastases by antagonizing cancer cell non-canonical WNT/PCP-RAC1-JNK signalling. In the lungs, DKK1 also inhibits WNT/Ca2+-CaMKII-NF-kappaB signalling and suppresses LTBP1-mediated TGF-beta secretion of cancer cells. In contrast, DKK1 promotes breast-to-bone metastasis by regulating canonical WNT signalling of osteoblasts. Importantly, targeting canonical WNT may not be beneficial to treatment of metastatic cancer, while combinatory therapy against JNK and TGF-beta signalling effectively prevents metastasis to both the lungs and bone. Thus, DKK1 represents a class of Janus-faced molecules with dichotomous roles in organotropic metastasis, and our data provide a rationale for new anti-metastasis approaches. |
