Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-catenin signaling.

Misexpression of wingless-related MMTV integration site 5A in mouse mammary gland inhibits the milk ejection response and regulates connexin43 phosphorylation.

Wingless-related MMTV integration site 5A (Wnt5a) is a noncanonical signaling WNT that is expressed in every stage of mouse mammary gland development except lactation. Using slow release pellets containing WNT5A as well as Wnt5a-null tissue, we previously showed that WNT5A acts to limit mammary development. Here, we generated transgenic mice that overexpress WNT5A in the mammary epithelium using the mouse mammary tumor virus promoter (M5a mice).

Wnt5a as an effector of TGFβ in mammary development and cancer.

Wnt5a is a member of the Wingless-related/MMTV-integration family of secreted growth factors, which are involved in a wide range of cellular processes. Wnt signaling can be broadly divided into two categories the canonical, ß-catenin-dependent pathway and the non-canonical ß-catenin-independent pathway. Wnt5a is a non-canonical signaling member of the Wnt family.

Inhibiting breast cancer progression by exploiting TGFbeta signaling.

Transforming Growth Factor beta (TGFbeta) signaling influences most aspects of cellular function in addition to playing a major role in organ development, remodeling, and repair. Given the wide range of effects induced by TGFbeta, it is not surprising that alterations in TGFbeta signaling have been implicated in development and progression of many different cancer types. Within the context of breast cancer itself, TGFbeta is known to have a dual nature, being both tumor-suppressive during early breast cancer development and tumor-promoting during breast cancer metastasis.

Loss of TGF-beta or Wnt5a results in an increase in Wnt/beta-catenin activity and redirects mammary tumour phenotype.

Introduction: The tumour-suppressive effects of transforming growth factor-beta (TGF-beta) are well documented; however, the mechanistic basis of these effects is not fully understood. Previously, we showed that a non-canonical member of the Wingless-related protein family, Wnt5a, is required for TGF-beta-mediated effects on mammary development. Several lines of evidence support the hypothesis that Wnt5a acts as a tumour suppressor.