WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines

What is it about?

Recent clinical and molecular data suggests that the estrogen receptor signals via unique mechanisms in invasive lobular carcinoma (ILC), a subtype of breast cancer, relative to other breast cancers. Importantly, these different ER-driven mechanisms may be associated with clinical resistance to endocrine therapy - improved understanding of how ER works in ILC is critical to improving therapeutic options. We identified a signaling protein, WNT4, that is controlled by estrogen/ER specifically in ILC cells. WNT4 not only is necessary for how ILC cells respond to estrogen, but it can also drive resistance to anti-estrogen (endocrine) therapies. In this study, we describe how WNT4 is controlled by ER, and identify components of WNT4 signaling. WNT4 and its related signaling pathways represent novel therapeutic targets to improve endocrine therapy for ILC patients.

Featured Image

Why is it important?

Despite the fact that the identification of ILC is routinely part of a clinical diagnosis of breast cancer, there are no specific therapeutic options for ILC patients. To develop ILC-specific therapies, we need to understand the unique biology of ILC cells, in particular with regard to the estrogen receptor in ILC. Our study, proceeding our prior study on ER function in ILC (Sikora, Cancer Research 2014), lays a foundation for understanding the mechanisms of the unique functions of ER in ILC, and identifies potential targets for therapeutic development (ie WNT4 signaling).