WNT10B (Wingless-Type MMTV Integration Site Family)

WNT10B is a member of the WNT ligand gene family encoding a secreted growth factor that has been reported to have role in a wide range of biological actions. Wnt10b was originally identified from mouse embryos and the virgin mammary gland, the locus was cloned by retroviral insertional activation, similar to the strategy used to identify other mammary oncogenes. During mammary gland development, Wnt10b seems to play a relevant role as it is the earliest expressed Wnt ligand. It has been well established that transgenic expression of Wnt10b in mouse mammary epithelial cells under the control of the MMTV promoter leads to mammary gland hyperplasia, increased proliferation, and branching. Furthermore, WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of triple-negative breast cancer. The role of Wnt10b in immune system was first described in helper T cells, and its expression in preB and proB cell lines suggested an involvement in lymphoid development. Furthermore, in CD8 T cells Wnt10b is induced by parathyroid hormone (PTH), suggesting that Wnt10b is playing an important role in T-cell development nad function. In a different study increased levels of Wnt10b in the bone marrow were found in a regenerative model, in which both the stromal cells and HSCs had increased Wnt10b expression in response to injury. Insight into regenerative processes point to WNT10B as a candidate potentially linking tissue regeneration and cancer. Recently reported evidences support a role of the hematopoietic regeneration-associated WNT10B on AC133+ cells in human Acute Myeloid Leukemia (AML) via a recurrent rearrangement promoted by a mobile human transposable-WNT10B oncogene (ht-WNT10B), as a relevant mechanism for WNT10B involvement in human cancer.