Bronchoscopists should try to recognize the factors that influence patient satisfaction and adjust their management accordingly.

The phosphatases of regenerating liver (PRLs) are a unique family of plasma membrane-associated protein tyrosine phosphatases that have been hypothesized to be involved in metastatic cancer. How PRLs control cancer cell migration, invasion, and proliferation remains largely unknown. In the current study, we demonstrate a role for PRL-1 in the regulation of filamentous actin dynamics, which could promote cell metastatic processes. Human A549 non-small-cell lung cancer cells stably expressing wild-type PRL-1 exhibited a 60% increase in migration and a 3-fold increase in invasion. Cells expressing catalytic mutants of PRL-1 (C104S and D72A) lacked increased cell migration and invasion, indicating that these phenotypic changes required PRL-1 phosphatase activity. In contrast, PRL-1 small interfering RNA decreased in vitro lung cancer cell migration and invasion. The cadherin-catenin complex and dynamic filamentous actin are believed to control cellular invasiveness. Expression of wildtype PRL-1, but not phosphatase-inactive PRL-1 (C104S or D72A), decreased E-cadherin, vinculin, and paxillin expression. Ectopic expression of wild-type PRL-1 increased RhoA levels, which have an important role in actin filament assembly and stabilization of focal adhesion, and decreased activated Cdc42 and Rac. The Rho-associated protein kinaseRhoA activity, actin filament levels, and cellular migration and invasion in PRL-1-expressing cells. These results suggest that PRL-1 could be a productive cancer therapeutic target and support further efforts to identify its substrates.In the United States, lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for Ͼ165,000 deaths per year, and it is predicted to become the leading cause of death worldwide (Jemal et al., 2008). The 5-year survival rate remains at Ͻ15%, even though there have been numerous attempts to control mortality from lung cancer (Jemal et al., 2008). The fundamental cause of patient death is the invasive and metastatic properties of tumors, processes about which we have incomplete understanding and for which we have no targeted drugs.Tumor cell invasion and metastasis are dynamic cellular processes that extensively exploit phospho-relay signaling systems. The central role of abnormal protein tyrosine phosphorylation in human cancers is well accepted. The phosphatases of regenerating liver (PRLs) family represents a unique protein tyrosine phosphatase (PTP) subfamily with its three family members (PRL-1, PRL-2, and PRL-3) being the only PTPs that are subject to prenylation. Emerging evidence supports a role for PRLs in the basic biology of cancer cell development and metastasis (Stephens et al., 2005;Bessette et al., 2008).PRL-1 (also known as PTP4A1 and PTPCAAX) was first identified as a low-molecular-weight immediate-early gene, the expression of which was induced in rat regenerating liver (Mohn et al., 1991). PRL-1 exploits a catalytic cysteine and an aspartic acid during protein dephosphorylation. Its catalytic pocket is unus...

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Our data indicate that maspin has prognostic significance for pulmonary adenocarcinoma. A better understanding of the role of maspin in tumor suppression may be helpful for development of novel chemotherapies for patients with this deadly tumor.