Cell polarity is a fundamental property of all cells and plays important roles during multiple cellular processes during normal development and cancer. However, the roles cell polarity proteins play during normal development and carcinoma progression are not well understood. I will discuss our findings on the role played by two polarity proteins PARD3 and SCRIBBLE.
PARD3 is a member of the Par cell polarity protein complex that consists of PARD6/aPKC/PARD3. We find that loss of expression of the cell polarity protein PARD3 compromises cell-cell cohesion between epithelial cells and promotes metastatic behavior in the absence of an overt mesenchymal transition. I will discuss our recent methods to study cell-cell junction dynamics and cell differentiation status to investigate their role during cancer cell metastasis.
SCRIBBLE is a scaffolding protein that localizes to cell-cell junctions and cell membranes. I will briefly discuss our findings on the mechanisms by which SCRIBBLE regulates cancer initiation. In addition, I will discuss our recent observations on the role played by SCRIBBLE during normal mammary gland development. We have discovered that SCRIBBLE is required for membrane trafficking of prolactin receptor and prolactin-induced JAK2 and STAT5 activation, cell proliferation and milk protein gene expression. Loss of SCRIBBLE significantly inhibits prolactin-regulated biology such as lobuloalveolar development and lactation in mice. Thus SCRIBBLE is emerging to be an important regulator of the biology of cancer and normal cells.