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Breast cancer pak4

Chetan K Rane, Misaal Patel, Li Cai, William Senapedis, Erkan Baloglu, Audrey Minden
The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers, including breast cancer. Overexpression of PAK4 is sufficient to cause mouse mammary epithelial cells (iMMECs) to become tumorigenic. To gain insight into the long-term gene expression changes that occur downstream to PAK4, we performed Next Generation Sequencing of RNA collected from PAK4 overexpressing iMMECs and wild-type iMMECs. We identified a list of genes whose expression levels were altered in response to PAK4 overexpression in iMMECs...
October 18, 2017: Genomics
Li-Fang He, Hong-Wu Xu, Min Chen, Zhi-Rong Xian, Xiao-Fen Wen, Min-Na Chen, Cai-Wen Du, Wen-He Huang, Jun-Dong Wu, Guo-Jun Zhang
The p21-activated kinase 4 (PAK4) is sufficient to transform noncancerous mammary epithelial cells and to form tumors in the mammary glands of mice. The accumulated information suggests that PAK4 might be an oncogenic protein in breast cancer. In this study, we sought to identify the role for PAK4 in breast cancer progression. Immunohistochemical study revealed that high PAK4 expression is associated with larger tumor size, lymph node metastasis, and advanced stage cancer in 93 invasive breast carcinoma patients...
March 14, 2017: Oncotarget
Chetan Rane, William Senapedis, Erkan Baloglu, Yosef Landesman, Marsha Crochiere, Soumyasri Das-Gupta, Audrey Minden
Breast cancer is a heterogeneous disease consisting of several subtypes. Among these subtypes, triple negative breast cancer is particularly difficult to treat. This is due to a lack of understanding of the mechanisms behind the disease, and consequently a lack of druggable targets. PAK4 plays critical roles in cell survival, proliferation, and morphology. PAK4 protein levels are high in breast cancer cells and breast tumors, and the gene is often amplified in basal like breast cancers, which are frequently triple negative...
February 15, 2017: Scientific Reports
Yanqing Bi, Mengzi Tian, Jinghong Le, Linlin Wang, Xiaofang Liu, Jianhua Qu, Min Hao
BACKGROUND: Previous evidence have demonstrated that p21-activated kinase PAK4 was correlated with breast cancer. The aim of this paper is to study the expression and interaction of p21-activated kinase (pAK)-4 and P54 protein in breast cancer. METHODS: A total of 80 patients were enrolled in our study (breast fibroma n = 20, breast noninvasive cancer n = 20, early breast invasive cancer n = 20, and advanced breast invasive cancer). The expression of PAK4 was detected by immunohistochemical S-P method, and the relationship between them and the different pathological characteristics were compared...
June 13, 2016: World Journal of Surgical Oncology
Anna E Dart, Gary M Box, William Court, Madeline E Gale, John P Brown, Sarah E Pinder, Suzanne A Eccles, Claire M Wells
P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in a kinase-dependent manner. We found that PAK4 expression is significantly higher in high-grade human breast cancer patient samples, whereas depletion of PAK4 modifies cell adhesion dynamics of breast cancer cells. Surprisingly, systematic analysis of PAK4 functionality revealed that PAK4-driven adhesion turnover is neither dependent on Cdc42 binding nor kinase activity. Rather, reduced expression of PAK4 leads to a concomitant loss of RhoU expression...
November 23, 2015: Journal of Cell Biology
Ting Zhuang, Jian Zhu, Zhilun Li, Julie Lorent, Chunyan Zhao, Karin Dahlman-Wright, Staffan Strömblad
Estrogen receptor alpha (ERα) is highly expressed in most breast cancers. Consequently, ERα modulators, such as tamoxifen, are successful in breast cancer treatment, although tamoxifen resistance is commonly observed. While tamoxifen resistance may be caused by altered ERα signaling, the molecular mechanisms regulating ERα signaling and tamoxifen resistance are not entirely clear. Here, we found that PAK4 expression was consistently correlated to poor patient outcome in endocrine treated and tamoxifen-only treated breast cancer patients...
December 22, 2015: Oncotarget
Widyawilis Selamat, Pei-Ling Felicia Tay, Yohendran Baskaran, Ed Manser
The serine/threonine kinase PAK4 is a Cdc42 effector whose role is not well understood; overexpression of PAK4 has been associated with some cancers, and there are reports that correlate kinase level with increased cell migration in vitro. Here we report that PAK4 is primarily associated with cell-cell junctions in all the cell lines we tested, and fails to accumulate at focal adhesions or at the leading edge of migrating cells. In U2OS osteosarcoma and MCF-7 breast cancer cell lines, PAK4 depletion did not affect collective cell migration, but affected cell polarization...
2015: PloS One
Jae Young So, Hong Jin Lee, Pavel Kramata, Audrey Minden, Nanjoo Suh
Breast cancer is a heterogeneous disease that develops through a multistep process whose molecular basis remains poorly understood. The molecular mechanisms of breast cancer progression have been extensively studied using the MCF10 model. We summarized recent results on differential expression of proteins in the MCF10 cell series - MCF10A, MCF10AT1, and MCF10CA1a - and compared the ability of the latter 3 lines to form tumors in immunodeficient mice. In addition, we also investigated expression of several key signaling proteins in the MCF10 cell series corresponding to different stages of breast cancer progression...
January 1, 2012: Molecular and Cellular Pharmacology
Yanshu Li, Di Wang, Hongyan Zhang, Chunyu Wang, Wei Dai, Zhenguo Cheng, Guanqiao Wang, Feng Li
The p21-activated kinases have been implicated in the control of cell cycle progression. However, the biological mechanism underlying the role of p21-activated kinase 4 (PAK4) in cell cycle control remains unknown. Here, by using quantitative RT-PCR and immunoblot analyses, we discovered that over-expression of PAK4 could suppress cyclin-dependent kinase inhibitor 1C (p57(Kip2) ) expression in the MCF-7 human breast cancer cell line, whereas lentiviral vector-mediated small interfering RNA (siRNA) knockdown of PAK4 markedly promoted p57(Kip2) expression in MCF-7 cells...
October 2013: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
L E Wong, N Chen, V Karantza, A Minden
The Pak4 protein kinase, normally expressed at low level in the mammary gland, is commonly overexpressed in breast cancer. Overexpression of Pak4 transforms mouse mammary epithelial cells in vitro and renders these cells tumorigenic in athymic mice in vivo. Here we show that Pak4 is also required for oncogenic transformation of the human breast cancer cell line MDA-MB-231. These high Pak4-expressing human breast cancer cells form highly disorganized three-dimensional (3D) structures in vitro and readily give rise to orthotopic xenograft tumors in nude mice...
2013: Oncogenesis
Audrey Minden
Paks4, along with Paks5, and 6 are members of the group B family of p21-activated kinases (Paks). The Paks play multiple different roles in controlling cell morphology, cell growth, proliferation, and signaling. Pak4 has essential roles in embryonic development (Qu et al., 2003), but in adults high levels of Pak4 are frequently associated with cancer. Pak4 has been implicated in several types of cancer (Wells and Jones, 2010; Eswaran et al., 2009; Liu et al., 2008; and Liu et al., 2010) and it is strongly linked to breast cancer (Liu et al...
2012: ISRN Oncology
Y Liu, N Chen, X Cui, X Zheng, L Deng, S Price, V Karantza, A Minden
The Pak4 serine/threonine kinase is highly expressed in many cancer cell lines and human tumors. Although several studies have addressed the role for Pak4 in transformation of fibroblasts, most human cancers are epithelial in origin. Epithelial cancers are associated not only with changes in cell growth but also with changes in the cellular organization within the three-dimensional (3D) architecture of the affected tissues. In this study we used immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the role for Pak4 in mammary tumorigenesis...
November 4, 2010: Oncogene
Jannik N Andersen, Sriram Sathyanarayanan, Alessandra Di Bacco, An Chi, Theresa Zhang, Albert H Chen, Brian Dolinski, Manfred Kraus, Brian Roberts, William Arthur, Rich A Klinghoffer, Diana Gargano, Lixia Li, Igor Feldman, Bethany Lynch, John Rush, Ronald C Hendrickson, Peter Blume-Jensen, Cloud P Paweletz
Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR)...
August 4, 2010: Science Translational Medicine
Jin-xing Yang, Yu-jing Han, Hang Zheng, Rong-cheng Luo
OBJECTIVE: To study the role of p21-activated kinase-4 (PAK4) in the occurrence, progression and metastasis of breast cancer. METHOD: PAK4 expression was detected in 35 cases of normal breast, 22 breast cystic hyperplasia, 28 breast adenofibroma, 37 breast cancer (including 7 non-invasive cancer, 9 early invasive cancer and 21 invasive cancer) and 13 metastatic breast cancer tissues using immunohistochemistry for a comparison of PAK4 expression and distribution...
May 2010: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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