Pak1/LIMK1/Cofilin Pathway Contributes to Tumor Migration and Invasion in Human Non-Small Cell Lung Carcinomas and Cell Lines

Abstract

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.

Potentially functional polymorphisms in PAK1 are associated with risk of lung cancer in a Chinese population

“…Emerging evidences have suggested that PAK1 plays an important role in carcinogenesis and tumor progression . In special, for lung cancer PAK1 could promote cell motility, tumor migration, and invasion through different mechanism . Our current study provided genetic evidence at the population level that PAK1 may be involved in the carcinogenesis and development of lung cancer and further highlighted the important role of genetic variants in PAK1 as molecular biomarkers for lung cancer susceptibility.…”

“…Of interest, PAK1 was frequently implicated in the tumorigenesis and up‐regulation of PAK1 was frequently detected in various human cancers including lung cancer . Notably, PAK1 kinase can promote lung cancer cell motility, tumor migration, and invasion through activation of PAK1/LIMK1/cofilin pathway and CRK‐II serine phosphorylation . These evidence collectively revealed the importance of PAK1 in carcinogenesis, especially lung cancer.…”

Neural Wiskott-Aldrich syndrome protein (nWASP) is implicated in human lung cancer invasion

“…Squamous carcinoma cell types are more invasive and migratory compared with adenocarcinoma cells [25]. It has been shown here that nWASP expression correlates with more advanced lung cancer phenotypes and in particular lymph node metastasis.…”

Ursolic Acid Promotes Apoptosis of SGC-7901 Gastric Cancer Cells through ROCK/PTEN Mediated Mitochondrial Translocation of Cofilin-1

“…Cofilin is a member of ADF/cofilin family (Chen et al, 2010), it plays many important parts in apoptosis (Chua et al, 2003;Wang et al, 2008), differentiation (Zhou et al, 2012), invasion and migration (Jang et al, 2012;Popow-Wozniak et al, 2012), tumorigenesis (Polachini et al, 2012). Cofilin was found to translocate to mitochondria after staurosporine-induced apoptosis in neuroblastoma cells (Chua et al, 2003), or oxidantinduced apoptosis in neutrophils (Klamt et al, 2009).…”