Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells

Claire B. Pollock, Senji Shirasawa, Takehiko Sasazuki, Walter Kolch, Amardeep S. Dhillon

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

RAS oncegenes are thought to play a role at multiple stages of tumorigenesis. The role and mechanisms by which RAS oncogenes maintain the transformed state of human cancer cells are poorly understood. Here, we have studied the role of oncogenic K-RAS in maintaining cytoskeletal disruption, cell adhesion and motility in metastatic colon carcinoma cells. Targeted deletion of K-RASG13D from HCT116 colon carcinoma cells restored their ability to assemble stress fibers and focal adhesions/complexes, accompanied by increased cell-matrix adhesion and reduced motility. We further show that oncogenic K-Ras induces high Rho activity, but uncouples Rho from stress fiber formation. This uncoupling required the maintenance of high levels of the activator protein-1 family member, Fra-1, via a mitogen-activated protein/extracellular signal-regulated kinase-dependent pathway. We also show that PI3-icinase signaling is required for the motility of HCT116 cells downstream of oncogenic K-Ras. Our findings suggest that mutated K-RAS oncogenes are essential for maintenance of the transformed and invasive phenotype of human colon cancer cells.

Original languageEnglish
Pages (from-to)1244-1250
Number of pages7
JournalCancer Research
Volume65
Issue number4
DOIs
Publication statusPublished - Feb 15 2005
Externally publishedYes

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Colonic Neoplasms
Stress Fibers
Oncogenes
Colon
Cell-Matrix Junctions
HCT116 Cells
Carcinoma
Focal Adhesions
Aptitude
Extracellular Signal-Regulated MAP Kinases
Transcription Factor AP-1
Mitogens
Cell Adhesion
Cell Movement
Carcinogenesis
Maintenance
Phenotype
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. / Pollock, Claire B.; Shirasawa, Senji; Sasazuki, Takehiko; Kolch, Walter; Dhillon, Amardeep S.

In: Cancer Research, Vol. 65, No. 4, 15.02.2005, p. 1244-1250.

Research output: Contribution to journalArticle

Pollock, Claire B. ; Shirasawa, Senji ; Sasazuki, Takehiko ; Kolch, Walter ; Dhillon, Amardeep S. / Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. In: Cancer Research. 2005 ; Vol. 65, No. 4. pp. 1244-1250.
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