Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells

Abstract

Fer and its sperm and cancer specific variant, FerT, are non-receptor tyrosine kinases which play roles in cancer progression and metastasis. Recent studies have shed light on the regulatory role of these kinases in ensuring proper sperm function. Comparison of the regulatory cascades in which Fer and FerT are engaged in sperm and cancer cells presents an interesting picture, in which similar regulatory interactions of these enzymes are integrated in a similar or different regulatory context in the two cell types. These diverse compositions extend from the involvement of Fer in modulation of actin cytoskeleton integrity and function, to the unique regulatory interactions of Fer with PARP-1 and the PP1 phosphatase. Furthermore, recent findings link the metabolic regulatory roles of Fer and FerT in sperm and cancer cells. In the current review, we discuss the above detailed aspects, which portray Fer and FerT as new regulatory links between sperm and malignant cells. This perspective view can endow us with new analytical and research tools that will deepen our understanding of the regulatory trajectories and networks that govern these two multi-layered systems.

Mechanisms That Protect Mammalian Sperm from the Spontaneous Acrosome Reaction

“…Reactive oxygen species (ROS) are formed during sperm capacitation, which is important for the activation of CaMKII [12] and PLD [31]. Our group showed that treatment of bovine sperm with 50 µM H 2 O 2 causes a significant increase in CaMKII phosphorylation/activation, a state that is completely reversed by 100 µM H 2 O 2 [71]. In human sperm, the addition of SOD causes a decrease in the sAR [72].…”