title: PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell.
abstract: p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein-protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.forename: Shang-Nuan
authors.initials: SN
authors.lastname: Zhang
authors.forename: He-ya
authors.initials: HY
authors.lastname: Qian
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Pei
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; C443802:PAK5 protein, human; D054462:p21-Activated Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2