Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells
Cathepsin B protein and activity are known to localize to the basal plasma membrane of colon carcinoma cells following the appearance of K-ras mutations. Using immunofluorescence and subcellular fractionation techniques and two human colon carcinoma cell lines—one with a mutated K-ras allele (HCT 1...
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2003-11-01
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doaj-7b01dd8d5fc148b791ff940f86a0b1892020-11-24T21:47:24ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022003-11-015650751910.1016/S1476-5586(03)80035-0Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma CellsDora Cavallo-Medved0Julie Dosescu1Bruce E. Linebaugh2Mansoureh Sameni3Debbie Rudy4Bonnie F. Sloane5Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USA Cathepsin B protein and activity are known to localize to the basal plasma membrane of colon carcinoma cells following the appearance of K-ras mutations. Using immunofluorescence and subcellular fractionation techniques and two human colon carcinoma cell lines—one with a mutated K-ras allele (HCT 116) and a daughter line in which the mutated allele has been disrupted (HKh-2)—we demonstrate that the localization of cathepsin B to caveolae on the surface of these carcinoma cells is regulated by mutant K-ras. In HCT 116 cells, a greater percentage of cathepsin B was distributed to the caveolae, and the secretion of cathepsin B and pericellular (membrane-associated and secreted) cathepsin B activity were greater than observed in HKh-2 cells. Previous studies established the light chain of annexin II tetramer, p11, as a binding site for cathepsin B on the surface of tumor cells. The deletion of active K-ras in HKh-2 cells reduced the steady-state levels of p11 and caveolin-1 and the distribution of pl1 to caveolae. Based upon these results, we speculate that cathepsin B, a protease implicated in tumor progression, plays a functional role in initiating proteolytic cascades in caveolae as downstream components of this cascade (e.g., urokinase plasminogen activator and urokinase plasminogen activator receptor) are also present in HCT 116 caveolae. http://www.sciencedirect.com/science/article/pii/S1476558603800350Cancercysteine professesmembrane-associated professescaveolaeK-ras |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dora Cavallo-Medved Julie Dosescu Bruce E. Linebaugh Mansoureh Sameni Debbie Rudy Bonnie F. Sloane |
spellingShingle |
Dora Cavallo-Medved Julie Dosescu Bruce E. Linebaugh Mansoureh Sameni Debbie Rudy Bonnie F. Sloane Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells Neoplasia: An International Journal for Oncology Research Cancer cysteine professes membrane-associated professes caveolae K-ras |
author_facet |
Dora Cavallo-Medved Julie Dosescu Bruce E. Linebaugh Mansoureh Sameni Debbie Rudy Bonnie F. Sloane |
author_sort |
Dora Cavallo-Medved |
title |
Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells |
title_short |
Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells |
title_full |
Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells |
title_fullStr |
Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells |
title_full_unstemmed |
Mutant K-ras Regulates Cathepsin B Localization on the Surface of Human Colorectal Carcinoma Cells |
title_sort |
mutant k-ras regulates cathepsin b localization on the surface of human colorectal carcinoma cells |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2003-11-01 |
description |
Cathepsin B protein and activity are known to localize to the basal plasma membrane of colon carcinoma cells following the appearance of K-ras mutations. Using immunofluorescence and subcellular fractionation techniques and two human colon carcinoma cell lines—one with a mutated K-ras allele (HCT 116) and a daughter line in which the mutated allele has been disrupted (HKh-2)—we demonstrate that the localization of cathepsin B to caveolae on the surface of these carcinoma cells is regulated by mutant K-ras. In HCT 116 cells, a greater percentage of cathepsin B was distributed to the caveolae, and the secretion of cathepsin B and pericellular (membrane-associated and secreted) cathepsin B activity were greater than observed in HKh-2 cells. Previous studies established the light chain of annexin II tetramer, p11, as a binding site for cathepsin B on the surface of tumor cells. The deletion of active K-ras in HKh-2 cells reduced the steady-state levels of p11 and caveolin-1 and the distribution of pl1 to caveolae. Based upon these results, we speculate that cathepsin B, a protease implicated in tumor progression, plays a functional role in initiating proteolytic cascades in caveolae as downstream components of this cascade (e.g., urokinase plasminogen activator and urokinase plasminogen activator receptor) are also present in HCT 116 caveolae.
|
topic |
Cancer cysteine professes membrane-associated professes caveolae K-ras |
url |
http://www.sciencedirect.com/science/article/pii/S1476558603800350 |
work_keys_str_mv |
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