Supporting data for MOLECULAR MECHANISM OF MAMMARY GLAND DEVELOPMENT AND BREAST CANCER PROGRESSION

In this study, we first investigated the function of planar cell polarity (PCP) in mammary gland development. By genetic knockout or overexpression PCP core protein Vangl2, we found that PCP regulates mammary gland pubertal development and alveologenesis in mice. Loss of Vangl1 did not affect mammary gland development. However, loss of both Vangl1 and Vangl2 led to shorter mammary ducts and fewer branches. On the contrary, induced Vangl2 resulted in more small side branches. In addition, loss of both Vangl1 and Vangl2 led to smaller alveoli in reproductive cycle. 

After that, we turned to study breast cancer. We found that Kindlin-2, a focal adhesion-related protein, facilited Src-induced androgen receptor (AR) phosphorylation at tyrosine 534 site in the absence of androgen. Then, phosphorylated AR translocated to cell nucleus and induced the expression of AR target gene, such as cyclin D1, which promoted cell cycle G1/S phase transition, cell proliferation, and cell migration. Thus, Kindlin-2-Src-AR signaling regulates breast cancer progression.