Chapter Six - Myosins: Driving us towards novel targets and biomarkers in cancer
Section snippets
The myosin super-family
Myosins are a super-family of molecular motors organized in 18 classes based on their sequence similarity (Berg et al., 2001; Sellers, 2000). Among these, 12 classes are found in humans, whose genome contains near to 40 myosin genes (Berg et al., 2001; and see Table 1). Myosins use ATP as an energy source to produce a mechanical force and move along actin filaments. They were first discovered in skeletal muscle (Hartman and Spudich, 2012; Kühne, 1864) but, later on, they were also found to be
The role of myosins in health and diseases
While myosins were first considered only for their role in muscle contraction, their expression pattern suggested alternative functions. This is best exemplified by Myosin II which contracts the cleavage furrow during cell division. Indeed, it was observed already several decades ago that blocking Myosin II impairs cytokinesis (De Lozanne and Spudich, 1987; Mabuchi and Okuno, 1977; Matsumura, 2005). As myosins represent actin binding proteins, the organization of many subcellular actin
Myosins in cancer
Myosins have been identified as potential key players in the initiation, progression and/or dissemination of cancer. Gene mutation screening in tumors for instance highlighted myosins as possible malignancy drivers as it was reported for MYO5B in pheochromocytomas (Wilzén et al., 2016). However, myosins can act as both, oncogenes and tumor suppressor genes. Indeed, some myosins have been described to favor tumor growth or spreading while others are able to limit their extent. It is noteworthy
Conclusion
Since the discovery of the first non-muscle myosin in the 1970s and the further identification of several additional classes, our view of myosins evolved a lot during the last decades. It is now clear that in addition to trigger muscle contraction, they play major roles in multiple actin-based cellular aspects including cell division, migration and differentiation. Being regulators of vesicle trafficking enables them to control how cells interact with each other or with their environment. As a
Funding
This project was supported by the Foundation Cancer (F1R-LSC-PAU-13HY2C) and by a Proof of Concept grant (PoC18/12554295) through the FNR and by the Foundation Vera Nijs and Jens Erik Rosborg. E.L. is supported by a CORE grant (C16/BM/11282028). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this chapter.
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