The identification of protein tyrosine phosphatase 1B (PTP1B) as the first PTP (Tonks NK, 1988) opened a new field of research and since this landmark discovery, over 107 different PTPs have been identified in the human genome (Alonso A, 2004). To date PTP1B remains the tyrosine phosphatase that has garnered the most interest in academic and industrial laboratories due to its striking effects on metabolism and more recently in cancer.
My laboratory has published several key papers analyzing the function of PTP1B. Specifically, in 1999, our Science paper described PTP1B as a negative regulator of the Insulin Receptor (Elchebly M, 1999).
This seminal work established that PTP1B was an outstanding target in type II diabetes and triggered a large involvement of pharmaceuticals and biotech in PTP1B inhibitor screens. In 2002, in back-to-back studies with B. Neel’s lab in Developmental Cell (Zabolotny JM, 2002), we reported that PTP1B modulates the leptin signaling pathway in the brain (Cheng A, 2002), thus establishing PTP1B as an exciting target in obesity. However, I was always surprised that although PTP1B was known as a receptor kinase down-regulator, the knockout PTP1B mice never developed tumors. Furthermore, this enzyme was often found overexpressed in human cancers.
Interestingly, our recent work on PTP1B allowed us to clearly establish that PTP1B provides a pro-oncogenic function in breast cancer (Julien SG, 2007). We also established potential molecular and signaling mechanism explaining its tumorigenic properties (Dubé N, 2004). To become more effective, cancer treatments are moving rapidly towards targeted therapy both at the level of tumor and patient genotypes. It is with this landscape in mind, that my current project is entirely dedicated to better understanding PTP1B function in cancer. We plan to examine directly its importance in breast and other human cancers, clarify its molecular action, develop new animal models for its study in cancer initiation and promotion, and finally validate its potential as a single target or in co-therapies in various human cancers.