Anti-LIMK2 polyclonal antibody

Background: LIM domain kinase 2 (LIMK2) plays an important role in cell proliferation, adhesion, migration, differentiation and inflammation. Abnormal expression of LIMK2 is implicated in various malignancies, but little is known about its expression and prognostic value in breast cancer. Methods: Specimens were collected from 212 patients for the analysis of LIMK2 expression by immunohistochemistry. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of LIMK2 in breast cancer. The same analyses were conducted using METABRIC and the Kaplan Meier plotter databases to validate the expression pattern and prognostic value of LIMK2. Results: LIMK2 was located in the cytoplasm, and the positive rate of LIMK2 expression in the breast cancer tissues was significantly higher than that in normal breast tissues (P<0.0001). Elevated LIMK2 expression correlated with large tumor size and high histological grade (P<0.05 for each). Kaplan-Meier analysis showed elevated expression of LIMK2 predicted worse disease-free survival (DFS) (HR: 3.295, 95% CI: 2.2517.156, P<0.0001) and overall survival (OS) (HR: 6.251, 95% CI: 3.874-16.260, P<0.0001). Multivariable Cox regression analysis indicated elevated expression of LIMK2 was an independent prognostic factor for both DFS and OS (for DFS, HR: 2.707, 95% CI: 1.546-4.740, P=0.0005; for OS, HR: 5.241, 95% CI: 2.436-11.277, P<0.0001). The expression pattern and prognostic significance of LIMK2 in breast cancer patients were validated by bioinformatics analysis of public databases. Conclusion: In conclusion, our results suggest that LIMK2 is an independent poor prognostic factor for breast cancer patients, and LIMK2 might play an important role in the progression of breast cancer.

The p53 tumor suppressor protein is widely known for its role as a sequence-specific transcription factor that regulates the expression of stress response genes. Here, we report the identification of LIMK2, which encodes a kinase that regulates actin dynamics through phosphorylation of cofilin, as a p53 target upregulated by DNA damage. Interestingly, the splice variant LIMK2b, but not LIMK2a, was induced in a p53-dependent manner through an intronic consensus p53-binding site. Depletion of LIMK2b leads to early exit of G2/M arrest after DNA damage, whereas its overexpression prolongs the arrest. These responses are recapitulated by ectopic expression of the active cofilin S3A mutant and the inactive cofilin S3D mutant, respectively, suggesting that LIMK2b may modulate G2/M arrest through cofilin phosphorylation. Furthermore, in support of its potential role as a tumor suppressor, LIMK2b was downregulated in esophageal and thyroid cancers, as well as in a number of established cancer cell lines, and its expression suppresses cancer cell migration. Taken together, our results unveil a novel pathway whereby LIMK2b, acting downstream of p53, ensures proper execution of checkpoint arrest by modulating the dynamics of actin polymerization. Oncogene (2010) 29, 2864-2876; doi: 10.1038/onc.2010.40; published online 1 March 2010