Fig. 8: Pharmacological inhibition of SPRK1 or LIMK2 inhibits metastatic characteristics of TNBC.

a Firefly luciferase–labeled MDA-MB-231 cells (MDA-MB-231-F-Luc) were injected subcutaneously into NSG mice (n = 4/group). From week 4, mice were treated orally with the vehicle (0.5% methyl cellulose in PBS) or 50 mg/kg LX7101 (in 0.5% methyl cellulose in PBS) every other day. Tumor volumes for mice were measured and plotted each week. Week 4 data includes four vehicle-treated mice and four drug-treated mice. b Imaged lungs of the mice killed at the end of the experiment presented in a. c Percentage incidence of metastasis is presented in indicated groups. Contingency analysis using Fisher’s exact test shows statistically significant difference in the incidence of metastasis between vehicle or LX7101 treatment. d A model showing the mechanism by which LIMK2 facilitates metastatic progression of TNBC. The model indicates that LIMK2 is necessary for distal metastasis of TNBC and functions, in part, by phosphorylating and increased the kinase activity of SRPK1. Data in a is presented as the means ± SD. ns not significant P-value, ****P < 0.0001.