Meddling with myosin’s mechanobiology in cancer

Nearly all cancers are diseases of uncontrolled cell growth coupled with dramatic changes in shape and motility. In fact, pathologists have used alterations in cellular and nuclear morphology to identify cancerous tissue for over a hundred years. These fundamental cellular processes—which in cancer also include invasion, dissemination, and secondary site formation—are driven and controlled by the cell’s cytoskeletal network. Embedded in and acting on the actin cytoskeleton, is the force-generating motor protein myosin II, which exists as 3 paralogs (NMIIA, IIB, and IIC) in mammalian, nonmuscle cells. Because of the fundamental nature of these processes, a long-held belief in the cancer field is that components of the cytoskeletal network do not make good targets for anticancer therapy development, despite their altered expression and function in many types of cancer (e.g., refs. 1 and 2). However, Picariello et al. (3) demonstrate that targeting nonmuscle myosin II can be a very effective strategy but must be done in conjunction with targeting additional growth pathways.Targeting myosin II proteins has always seemed problematic for 2 main reasons. First, the classic textbook view of myosin II has the protein conducting only one major role in the cell: to generate and drive contractility by pulling on antiparallel actin filaments. This simplified … [↵][1]1To whom correspondence may be addressed. Email: dnr{at}jhmi.edu or asurcel1{at}jhmi.edu. [1]: #xref-corresp-1-1