Cancer Cell Biology
Area of interest
Our research focuses on the cytoskeletal cell biology underlying invasion, metastasis, and angiogenesis. Much of our current research centers on myosin-X (Myo10), a molecular motor that has central roles in the finger-like cellular protrusions known as filopodia. Myo10 is also a key component of invadopodia, the actin-based protrusions that cancer cells use to invade their surroundings. Myo10 binds to and is activated by PIP3, a crucial signaling lipid that is upregulated in most cancers, and Myo10 appears to function as a filopodial effector for PIP3. Exciting recent work shows that Myo10 is a key protein for invasion in major forms of cancer, including breast, lung, and melanoma. We have shown that Myo10 can bind to microtubules and is involved in spindle orientation, and cancer cells have been reported to require Myo10 to successfully divide in the presence of the multiple centrosomes that are a hallmark of most cancers. We have also recently discovered that an unusual motorless form of Myo10 is expressed primarily in neural and embryonic stem cells. Our laboratory’s expertise in cytoskeletal cell biology, live cell imaging, and our extensive tool set for investigating myosins provides a firm foundation to investigate the fundamental biology of cancer and to work with the Lineberger Cancer Cell Biology program to translate these discoveries into improved cancer treatments.
Awards and Honors
- Our research measuring the molecular step size of brain myosin-Va (Myo5a) and demonstrating that Myo5a is a processive myosin has had a large impact on the motor protein field and has led to insights on the fundamental mechanisms of force production.
- We also discovered a new member of the myosin-V family, myosin-Vc (Myo5c), which appears to be the major class V myosin in many non-neuronal tissues.
- Our discovery of Myo10 is of particular relevance to cancer cell biology due to the probable roles of this protein in cell adhesion, PI(3) kinase signaling, and intrafilopodial motility. This research has also led us to identify a putative filopodial tip complex and raises important questions about the structure and biology of filopodia. To identify the full set of candidate motors responsible for actin-based movements in human and several other organisms, we also performed a systematic and exhaustive genome-based analysis. In human alone we discovered evidence for the existence of 8 novel myosin genes, including 2 myosins-I and 3 conventional myosins. Importantly, one of the conventional myosins is a previously unsuspected non-muscle myosin-II, a protein that has been intensively studied by cell and cancer biologists because of its role in cytokinesis and cell motility.
- Our lab was recently honored by a 2002 Hettleman prize for scholarly and artistic contributions by UNC faculty.