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Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway

Oncogene volume 20, pages 2112–2121 (2001)Cite this article

Abstract

Tropomyosin (TM) family of cytoskeletal proteins is implicated in stabilizing actin microfilaments. Many TM isoforms, including tropomyosin-1 (TM1), are down-regulated in transformed cells. Previously we demonstrated that TM1 is a suppressor of the malignant transformation, and that TM1 reorganizes microfilaments in the transformed cells. To investigate how TM1 induces microfilament organization in transformed cells, we utilized ras-transformed NIH3T3 (DT) cells, and those transduced to express TM1, and/or TM2. Enhanced expression of TM1 alone, but not TM2, results in re-emergence of microfilaments; TM1, together with TM2 remarkably improves microfilament architecture. TM1 induced cytoskeletal reorganization involves an enhanced expression of caldesmon, but not vinculin, α-actinin, or gelsolin. In addition, TM1-induced cytoskeletal reorganization and the revertant phenotype appears to involve re-activation of RhoA controlled pathways in DT cells. RhoA expression, which is suppressed in DT cells, is significantly increased in TM1-expressing cells, without detectable changes in the expression of Rac or Cdc42. Furthermore, expression of a dominant negative Rho kinase, or treatment with Y-27632 disassembled microfilaments in normal NIH3T3 and in TM1 expressing cells. These data suggest that reactivation of Rho kinase directed pathways are critical for TM1-mediated microfilament assemblies.

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Acknowledgements

We thank Dr Fumio Matsumura of Rutgers University for providing caldesmon cDNA probes and for helpful suggestions, and Yoshitomi Pharmaceuticals for supplying us with Y-27632. We thank Dr Steve Cosenza of the Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia for his help with the confocal microscopy. This work was supported by grants from American Heart Association (Pennsylvania Affiliate) and WW Smith Charitable Trust, Philadelphia. GL Prasad is also a recipient of a career development award (DAMD17-98-1-8162) from the US Army Breast Cancer Research Program.

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Authors and Affiliations

  1. Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, NC, USA

    Shantaram Bharadwaj & G L Prasad

  2. Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, NC, USA

    Shantaram Bharadwaj & G L Prasad

  3. Wistar Institute of Anatomy and Cell Biology, Philadelphia, Pennsylvania, USA

    Vanya Shah

  4. Nara Institute of Science and Technology Ikoma, Japan

    Kozo Kaibuchi

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  1. Vanya Shah
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Shah, V., Bharadwaj, S., Kaibuchi, K. et al. Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway. Oncogene 20, 2112–2121 (2001). https://doi.org/10.1038/sj.onc.1204291

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