1. ERM proteins promote CD44 cleavage.
ERM proteins promote CD44 cleavage. A, downregulation of all 3 ERM proteins reduce CD44 cleavage. RPM-MC cells were transfected as in Fig. 1A. Cells were grown at low density. The expression of ERM proteins was downregulated in about 98% of the cells by a mixture of siRNAs targeting all 3 members of the ERM protein family, ezrin, radixin, and moesin (nontargeting siRNA “C” was used as control). Downregulation of ERM proteins inhibited ectodomain cleavage of CD44. B, NRG1 cleavage is resistant to downregulation of ERM proteins. Setup of the experiment as in A, except that double-tagged NRG1 was transfected as cleavage substrate. C, constitutive activation of the Ras pathway does not stimulate CD44 cleavage. Overexpression of an HA-tagged dominant active SOS mutant (DA-SOS, 24) that is permanently membrane-associated, activates Ras—as detected by phosphorylated Erk—independently of the presence of ERM proteins and TPA treatment. Histogram shows mean values of relative level of solCD44E ± SD from 3 independent experiments (Wt: V vs. DA-SOS, P = ; KR-Mt: V vs. DA-SOS, P = ).
Monika Hartmann et al. Mol Cancer Res 2015;13:
©2015 by American Association for Cancer Research