| First Author | Borcherding N | Year | 2015 |
| Journal | Cancer Res | Volume | 75 |
| Issue | 10 | Pages | 1972-82 |
| PubMed ID | 25769722 | Mgi Jnum | J:221120 |
| Mgi Id | MGI:5638268 | Doi | 10.1158/0008-5472.CAN-14-2761 |
| Citation | Borcherding N, et al. (2015) Paracrine WNT5A Signaling Inhibits Expansion of Tumor-Initiating Cells. Cancer Res 75(10):1972-82 |
| abstractText | It is not well understood how paracrine communication between basal and luminal cell populations in the mammary gland affects tumorigenesis. During ErbB2-induced mammary tumorigenesis, enriched mammary stem cells that represent a subpopulation of basal cells exhibit enhanced tumorigenic capacity compared with the corresponding luminal progenitors. Transcript profiling of tumors derived from basal and luminal tumor-initiating cells (TIC) revealed preferential loss of the noncanonical Wnt ligand WNT5A in basal TIC-derived tumors. Heterozygous loss of WNT5A was correlated with shorter survival of breast cancer patients. In a mouse model of ErbB2-induced breast cancer, Wnt5a heterozygosity promoted tumor multiplicity and pulmonary metastasis. As a TGFbeta substrate, luminal cell-produced WNT5A induced a feed-forward loop to activate SMAD2 in a RYK and TGFbetaR1-dependent manner to limit the expansion of basal TIC in a paracrine fashion, a potential explanation for the suppressive effect of WNT5A in mammary tumorigenesis. Our results identify the WNT5A/RYK module as a spatial regulator of the TGFbeta-SMAD signaling pathway in the context of mammary gland development and carcinogenesis, offering a new perspective on tumor suppression provided by basal-luminal cross-talk in normal mammary tissue. Cancer Res; 75(10); 1972-82. (c)2015 AACR. |
