This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Podosomes are actin-rich projections of the cell membrane that are associated with cancer cell migration and metastases. Their formation requires rearrangements of the actin cytoskeleton, which are mediated through the interaction of a host of actin-binding proteins. Tumor-promoting phorbol esters cause actin cytoskeletal rearrangements that result in podosome formation in a variety of cell types;including vascular smooth muscle cells, osteoclasts, macrophages, endothelial cells, neural cells myoblasts and transformed fibroblasts. Tumor-promoting phorbol esters function by activating one or more PKC isoforms, resulting in the reorganization of the actin cytoskeleton and src activation AFAP-110, an adaptor protein that cross-links actin filaments, activates src in response to phosphorylation by PKC-a and is involved in podosome formation. Increased levels of AFAP-110 are correlated with increases in podosome lifetime in A7r5 tumor cells and prostate cancer. Although the role of AFAP-110 as a src activator is well established, the mechanism by which activated AFAP-110 is itself regulated remains incompletely characterized. Scaffolding proteins, such as Tks5, recruit AFAP-110 and other signaling proteins to podosomes. Homer2 is a scaffolding protein of the Vesl/Homer family that interacts with both actin filaments and activated Rho GTPases in mouse cerebellar cells and can prevent podosome formation in cdc42-activated HeLa cells. Homer2 has been identified as a binding partner for AFAP-110 in two independent yeast two-hybrid studies. We hypothesize that Homer2 is a binding partner and regulator for AFAP-110. In this proposal we will address the mechanism by which Homer2 abrogates podosome formation.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Marshall University
Schools of Medicine
United States
Zip Code
Zhang, Yu; Chen, Shiguo; Wei, Chaoyang et al. (2018) Dietary compound proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves attenuate chemotherapy-resistant ovarian cancer stem cell traits via targeting the Wnt/?-catenin signaling pathway and inducing G1 cell cycle arrest. Food Funct 9:525-533
Gao, Ying; Yin, Junfeng; Rankin, Gary O et al. (2018) Kaempferol Induces G2/M Cell Cycle Arrest via Checkpoint Kinase 2 and Promotes Apoptosis via Death Receptors in Human Ovarian Carcinoma A2780/CP70 Cells. Molecules 23:
Pan, Haibo; Li, Jin; Rankin, Gary O et al. (2018) Synergistic effect of black tea polyphenol, theaflavin-3,3'-digallate with cisplatin against cisplatin resistant human ovarian cancer cells. J Funct Foods 46:1-11
Zhang, Shichao; Xing, Malcolm M Q; Li, Bingyun (2018) Capsule Integrated Polypeptide Multilayer Films for Effective pH-Responsive Multiple Drug Co-Delivery. ACS Appl Mater Interfaces :
Zhang, Yu; Chen, Shiguo; Wei, Chaoyang et al. (2018) Flavonoids from Chinese bayberry leaves induced apoptosis and G1 cell cycle arrest via Erk pathway in ovarian cancer cells. Eur J Med Chem 147:218-226
Zhang, Yu; Chen, Shiguo; Wei, Chaoyang et al. (2018) Dietary Compound Proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves inhibit angiogenesis and regulate cell cycle of cisplatin-resistant ovarian cancer cells via targeting Akt pathway. J Funct Foods 40:573-581
Jia, Ling-Yan; Wu, Xue-Jin; Gao, Ying et al. (2017) Inhibitory Effects of Total Triterpenoid Saponins Isolated from the Seeds of the Tea Plant (Camellia sinensis) on Human Ovarian Cancer Cells. Molecules 22:
Pan, Haibo; Wang, Fang; Rankin, Gary O et al. (2017) Inhibitory effect of black tea pigments, theaflavin?3/3'-gallate against cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest. Int J Oncol 51:1508-1520
Kocher, Caitlin; Christiansen, Matthew; Martin, Sarah et al. (2017) Sexual dimorphism in obesity-related genes in the epicardial fat during aging. J Physiol Biochem 73:215-224
Alway, Stephen E; McCrory, Jean L; Kearcher, Kalen et al. (2017) Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women. J Gerontol A Biol Sci Med Sci 72:1595-1606

Showing the most recent 10 out of 199 publications