Role of c-MET in upper aerodigestive malignancies - From biology to novel therapies

Sascha Dietrich, Radha Uppalapati, Tanguy Y. Seiwert, Patrick C. Ma

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis.This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.

Original languageEnglish (US)
Pages (from-to)149-162
Number of pages14
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume24
Issue number3
DOIs
StatePublished - Dec 1 2005

Fingerprint

Cell Movement
Hepatocyte Growth Factor
Receptor Protein-Tyrosine Kinases
Neoplasms
Signal transduction
Cell proliferation
Morphogenesis
Reactive Oxygen Species
Signal Transduction
Carcinogenesis
Therapeutics
Down-Regulation
Chemical activation
Cell Proliferation
Scattering
Apoptosis
Neoplasm Metastasis
Ligands
Mutation
Survival

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

@article{7e7e6a44bdcc4205914ace83df098af5,
title = "Role of c-MET in upper aerodigestive malignancies - From biology to novel therapies",
abstract = "Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis.This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.",
author = "Sascha Dietrich and Radha Uppalapati and Seiwert, {Tanguy Y.} and Ma, {Patrick C.}",
year = "2005",
month = "12",
day = "1",
doi = "10.1615/JEnvPathToxOncol.v24.i3.20",
language = "English (US)",
volume = "24",
pages = "149--162",
journal = "Journal of Environmental Pathology, Toxicology and Oncology",
issn = "0731-8898",
publisher = "Begell House Inc.",
number = "3",

}

Role of c-MET in upper aerodigestive malignancies - From biology to novel therapies. / Dietrich, Sascha; Uppalapati, Radha; Seiwert, Tanguy Y.; Ma, Patrick C.

In: Journal of Environmental Pathology, Toxicology and Oncology, Vol. 24, No. 3, 01.12.2005, p. 149-162.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Role of c-MET in upper aerodigestive malignancies - From biology to novel therapies

AU - Dietrich, Sascha

AU - Uppalapati, Radha

AU - Seiwert, Tanguy Y.

AU - Ma, Patrick C.

PY - 2005/12/1

Y1 - 2005/12/1

N2 - Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis.This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.

AB - Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis.This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.

UR - http://www.scopus.com/inward/record.url?scp=25144439139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25144439139&partnerID=8YFLogxK

U2 - 10.1615/JEnvPathToxOncol.v24.i3.20

DO - 10.1615/JEnvPathToxOncol.v24.i3.20

M3 - Review article

C2 - 16050800

AN - SCOPUS:25144439139

VL - 24

SP - 149

EP - 162

JO - Journal of Environmental Pathology, Toxicology and Oncology

JF - Journal of Environmental Pathology, Toxicology and Oncology

SN - 0731-8898

IS - 3

ER -