Back to Search
Start Over
Pak-1 expression increases with progression of colorectal carcinomas to metastasis.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2004 May 15; Vol. 10 (10), pp. 3448-56. - Publication Year :
- 2004
-
Abstract
- Purpose: The p21-activated kinase-1 (Pak-1) promotes cell motility and invasiveness. Pak-1 is activated by the Rac, Rho, and Cdc42 small GTPases in response to a variety of stimuli including ras and phosphatidylinositol 3'-kinase/AKT pathway activation. Because Pak-1 plays a central role in regulating cell motility and invasiveness, we sought to determine whether Pak-1 may be involved in the malignant progression of colorectal carcinoma.<br />Experimental Design: Pak-1 expression was examined by immunohistochemistry in archived tissues from normal human colons, tubular and tubulovillous adenomas, invasive adenocarcinomas (stages I-III/IV), and lymph node metastases (184 total specimens from 38 patients). Specific cytoplasmic immunostaining was evaluated for overall intensity and uniformity to derive a combined histoscore (stain intensity x percentage of epithelium stained).<br />Results: Pak-1 expression was increased significantly with colorectal cancer progression from normal tissue to lymph node metastases (P < 0.0001). Furthermore, Pak-1 expression was increased significantly in adenomas, invasive carcinomas, and lymph node metastases compared with normal colon (P < 0.0001). Strikingly, Pak-1 expression was significantly higher in lymph node metastases than in invasive cancers, adenomas, or normal colon (P < 0.0001). Moreover, in patients with multiple lesions representing different stages of disease, Pak-1 expression was increased specifically in the most advanced lesions.<br />Conclusions: This study demonstrates that Pak-1 expression is increased significantly with malignant progression of human colorectal carcinoma. These data, along with numerous functional studies demonstrating a central role for Pak-1 activity in tumor invasiveness and motility, implicate Pak-1 as an exciting target for therapy of colorectal carcinoma.
- Subjects :
- Adenoma metabolism
Carcinoma metabolism
Colon pathology
Colonic Neoplasms pathology
Colorectal Neoplasms metabolism
Cytoplasm metabolism
Disease Progression
GTP Phosphohydrolases metabolism
Humans
Immunohistochemistry
Lymphatic Metastasis
Neoplasm Metastasis
Phosphatidylinositol 3-Kinases metabolism
Protein Serine-Threonine Kinases metabolism
Treatment Outcome
cdc42 GTP-Binding Protein metabolism
p21-Activated Kinases
ras Proteins metabolism
Colorectal Neoplasms pathology
Protein Serine-Threonine Kinases biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 15161701
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-03-0210