P21-activated kinase 5 (PAK5) is the recently identified member of the group B p21-activated kinase (PAK) family which are effectors of the small GTPase Cdc42 and Rac1, known to regulate cell motility and activate cell-survival signaling pathways. However, overexpression of PAK5 has not been associated with any cancers so far. Interestingly, we found that PAK5 was overexpressed in a variety of colorectal carcinoma (CRC) cell lines in a Western-blotting examination. Therefore, in this study, we aim to examine the PAK5 expression during CRC progression and to answer if PAK5 is involved in malignant progression of CRC. By immunohistochemistry, our results showed that PAK5 expression was increased with CRC progression through the adenoma to carcinoma sequence, with the most significant increases in invasive and metastatic CRCs (p < 0.0001). Furthermore, increased PAK5 expression was also found with the development of CRC from lower Duke's grades to higher ones (p < 0.01). Moreover, PAK5 was also increased from well to poorly differentiated CRCs (p < 0.01). Using gain and loss of function experiments, we found that PAK5 reduced CRC cell adhesion but promoted their migration on collagen type I. Taken together, our study demonstrated that PAK5 expression increased significantly with malignant progression of CRC and that PAK5 might promote CRC metastasis by regulating CRC cell adhesion and migration. ' UICCKey words: colorectal carcinoma; PAK5; cancer cell adhesion and migration P21-activated kinases (PAKs), a family of serine/threonine kinases, are small GTPase effectors that play important roles in regulating cell shape, movement, proliferation and survival. [1][2][3] PAKs are characterized by a highly conserved amino-terminal Cdc42/ Rac interactive binding (CRIB) domain and a carboxyl terminal kinase domain. [4][5][6] Six human PAKs were identified and divided into two groups based on their amino acid sequences and their functions. Group A PAKs (PAK1, 2 and 3) share 80 to 90% sequence identity within their catalytic domains, whereas the recently identified group B PAKs (PAK4, 5 and 6), show only approximately 50% identity to the kinase domains of the group A PAKs. 6,7 A marked difference between the two PAK groups is the autologous inhibitory sequence in the NH2-terminal regulatory domain found in group A PAKs, with no obvious homologous sequence in group B. 7 Unlike group A PAKs, whose binding of Cdc42 and Rac leads to their activation, Group B PAKs are not strongly activated by GTPase binding. 8 Of the three group B PAKs, PAK4 was the best characterized, involving in cell adhesion, migration, proliferation and activation of cell-survival pathways that lead to protection from apoptosis. 9,10 Our previous study demonstrated that PAK4 regulated integrin avb5-mediated breast carcinoma cell migration. 11 Different PAK family members have different tissue-specific expression patterns. PAK4 was found to be overexpressed in 78% of a variety of human cancer cell lines, 12 whereas PAK5 and PAK6 showed restricted tissue-spe...

Hepatocellular carcinoma ( HCC ) is one of the most common causes of cancer‐related death. Cytokines, including interleukin 24 ( IL ‐24), play an important role in HCC . IL ‐24 inhibits HCC metastasis but the molecular mechanism by which this occurs is still unknown. Micro RNA s (mi RNA s) are regulators of cancers including hepatocellular carcinoma ( HCC ). However, the role that mi RNA s play in the regulation of IL ‐24 in HCC is unclear. The aim of this study was to investigate the effects of regulation of IL‐24 by miR‐203a‐3p.1 on liver cancer cell proliferation and metastasis. IL ‐24 mRNA and miR‐203a‐3p.1 were detected by real‐time RT ‐ PCR , and IL ‐24 protein in the cell growth medium was measured by ELISA . A luciferase assay was used to verify that the IL ‐24 gene was the target of miR‐203a‐3p.1. Cell survival ability was detected by the MTT assay and colony formation. Cell metastasis was assayed by the Transwell system. The results showed that IL ‐24 could be down‐regulated by miR‐203a‐3p.1 in HCC cells and that miR‐203a‐3p.1 acted as an onco‐mi RNA by targeting IL ‐24. Inhibition of miR‐203a‐3p.1 in cells could lead to the reversal of HCC cell proliferation and metastasis. The study highlights a novel molecular interaction between miR‐203a‐3p.1 and IL ‐24, which indicates that IL ‐24 and miR‐203a‐3p.1 may constitute potential therapeutic targets for HCC .

Treatment strategies that include DAC present promising options for sensitizing breast cancer cells to irradiation.

Activated ras genes are found in a large number of human tumors, and therefore are one of important targets for cancer therapy. This study investigated the antitumor effects of a novel single chain fragment variable antibody (scFv) against ras protein, p21Ras. The anti-p21Ras scFv gene was constructed by phage display library from hybridoma KGHR1, and then subcloned into replication-defective adenovirus vector to obtain recombinant adenovirus KGHV100. Human tumor cell lines with high expression of p21Ras SW480, MDA-MB‑231, OVCAR-3, BEL-7402, as well as tumor cell line with low expression of p21Ras, SKOV3, were employed to investigate antitumor effects in vitro and in vivo. Fluorescence microscopy demonstrated that KGHV100 was able to express intracellularly anti-p21Ras scFv antibody in cultured tumor cells and in transplantation tumor cells. MTT, Transwell, colony formation, and flow cytometry analysis showed that KGHV100 led to significant growth arrest in tumor cells with high p21Ras expression, and induced G0/G1 cell cycle arrest in the studied tumor cell lines. In vivo, KGHV100 significantly inhibited tumor growth following intratumoral injection, and the survival rates of the mice were higher than the control group. These results indicate that the adenovirus-mediated intracellular expression of the novel anti-p21Ras scFv exerted strong antitumoral effects, and may be a potential method for therapy of cancers with p21Ras overexpression.