PMA-induced reduction in invasiveness is associated with hyperphosphorylation of MARCKS and talin in invasive bladder cancer cells Journal Article


Authors: Yokoyama, Y.; Ito, T.; Hanson, V.; Schwartz, G. K.; Aderem, A. A.; Holland, J. F.; Tamaya, T.; Ohnuma, T.
Article Title: PMA-induced reduction in invasiveness is associated with hyperphosphorylation of MARCKS and talin in invasive bladder cancer cells
Abstract: Protein kinase C (PKC) plays a critical role in signal transduction for a variety of cell activation processes. Enhanced PKC activity is often found in cancer cells that show marked invasive and/or metastatic potential. Thus, a specific PKC inhibitor may serve as a tool to reduce invasive or metastatic potential of cancer cells. We show here that phorbol 12-myristate 13-acetate (PMA), a PKC activator, also reduces invasiveness of EJ invasive transitional carcinoma cells. PMA-induced reduction in invasiveness was parallel with inhibition of cell motility. PMA neither induced E-cadherin expression nor augmented cell-matrix adhesion of EJ cells. PMA caused retraction of microspikes from the rim of the cells and consequently rounding of the cellular rim, and the disappearance of microfilaments from the cytoplasm. PMA at 10-7 M, at which concentration the motility of EJ cells was completely inhibited, down-regulated PKC activity over 5 hr after transient translocation of PKC activity to the membrane fraction. At the same time, PMA induced hyperphosphorylation of MARCKS and talin. During the process of cell movement, actin-binding proteins are in a cycle of phosphorylation and dephosphorylation. Once this cycle is interrupted, cells can no longer maintain the dynamics of cytoskeletal structure. We suggest that retention of the hyperphosphorylated scare of MARCKS and talin is responsible for the mechanism(s) by which PMA produces inhibitory activity against invasiveness of EJ cells.
Keywords: signal transduction; controlled study; protein phosphorylation; human cell; proteins; membrane proteins; cancer cell culture; tumor cells, cultured; phosphorylation; urinary bladder neoplasms; extracellular matrix; intracellular signaling peptides and proteins; cell membrane; cell movement; protein kinase c; invasive carcinoma; actin binding protein; neoplasm invasiveness; metastasis potential; bladder carcinoma; actins; cell adhesion; cadherins; transitional cell carcinoma; cell motility; protein kinase c inhibitor; phorbol 13 acetate 12 myristate; tetradecanoylphorbol acetate; vinculin; marcks protein; talin; protein kinase c activator; humans; human; priority journal; article
Journal Title: International Journal of Cancer
Volume: 75
Issue: 5
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 1998-03-02
Start Page: 774
End Page: 779
Language: English
DOI: 10.1002/(sici)1097-0215(19980302)75:5<774::aid-ijc18>3.0.co;2-6
PUBMED: 9495248
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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  1. Gary Schwartz
    385 Schwartz