Metastasis suppression by adiponectin: LKB1 rises up to the challenge

Neeraj K. Saxena, Dipali Sharma

Research output: Contribution to journalArticle

Abstract

Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options.Cancer research has largely focused on the molecular basis of oncogenic transformation and tumorigenesis for many years. Recent progress in cancer research has put the metastatic process at the center stage because higher metastatic potential of tumor cells is the major cause of mortality from solid tumors. Metastasis is a complex process that involves modulation of various molecular signaling networks. Tumor cells alter the microenvironment, attain greater cellular adhesion along with better ability to invade and migrate to gain access to circulation. These wandering tumor cells defy anoikis, survive in the circulation, exit into new permissive organ site and colonize distant organs.1 The microenvironment in which the tumor originates plays an important role in tumor initiation, progression and metastasis.

Original languageEnglish (US)
Pages (from-to)358-362
Number of pages5
JournalCell Adhesion and Migration
Volume4
Issue number3
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Adiponectin
Neoplasm Metastasis
AMP-Activated Protein Kinases
Breast Neoplasms
Neoplasms
Phosphorylation
Tumor Suppressor Genes
Carcinogenesis
Anoikis
Cellular Microenvironment
Acetyl-CoA Carboxylase
Adipokines
Therapeutics
Research
Insulin Resistance
Cardiovascular Diseases
Phosphotransferases
Up-Regulation
Obesity
Cell Proliferation

Keywords

  • Adiponectin
  • AMPK
  • Cancer
  • Invasion
  • LKB1
  • Migration
  • S6K

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience

Cite this

Metastasis suppression by adiponectin : LKB1 rises up to the challenge. / Saxena, Neeraj K.; Sharma, Dipali.

In: Cell Adhesion and Migration, Vol. 4, No. 3, 07.2010, p. 358-362.

Research output: Contribution to journalArticle

@article{539246813c794c1fb0abe6422bd29766,
title = "Metastasis suppression by adiponectin: LKB1 rises up to the challenge",
abstract = "Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options.Cancer research has largely focused on the molecular basis of oncogenic transformation and tumorigenesis for many years. Recent progress in cancer research has put the metastatic process at the center stage because higher metastatic potential of tumor cells is the major cause of mortality from solid tumors. Metastasis is a complex process that involves modulation of various molecular signaling networks. Tumor cells alter the microenvironment, attain greater cellular adhesion along with better ability to invade and migrate to gain access to circulation. These wandering tumor cells defy anoikis, survive in the circulation, exit into new permissive organ site and colonize distant organs.1 The microenvironment in which the tumor originates plays an important role in tumor initiation, progression and metastasis.",
keywords = "Adiponectin, AMPK, Cancer, Invasion, LKB1, Migration, S6K",
author = "Saxena, {Neeraj K.} and Dipali Sharma",
year = "2010",
month = "7",
doi = "10.4161/cam.4.3.11541",
language = "English (US)",
volume = "4",
pages = "358--362",
journal = "Cell Adhesion and Migration",
issn = "1933-6918",
publisher = "Landes Bioscience",
number = "3",

}

TY - JOUR

T1 - Metastasis suppression by adiponectin

T2 - LKB1 rises up to the challenge

AU - Saxena, Neeraj K.

AU - Sharma, Dipali

PY - 2010/7

Y1 - 2010/7

N2 - Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options.Cancer research has largely focused on the molecular basis of oncogenic transformation and tumorigenesis for many years. Recent progress in cancer research has put the metastatic process at the center stage because higher metastatic potential of tumor cells is the major cause of mortality from solid tumors. Metastasis is a complex process that involves modulation of various molecular signaling networks. Tumor cells alter the microenvironment, attain greater cellular adhesion along with better ability to invade and migrate to gain access to circulation. These wandering tumor cells defy anoikis, survive in the circulation, exit into new permissive organ site and colonize distant organs.1 The microenvironment in which the tumor originates plays an important role in tumor initiation, progression and metastasis.

AB - Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options.Cancer research has largely focused on the molecular basis of oncogenic transformation and tumorigenesis for many years. Recent progress in cancer research has put the metastatic process at the center stage because higher metastatic potential of tumor cells is the major cause of mortality from solid tumors. Metastasis is a complex process that involves modulation of various molecular signaling networks. Tumor cells alter the microenvironment, attain greater cellular adhesion along with better ability to invade and migrate to gain access to circulation. These wandering tumor cells defy anoikis, survive in the circulation, exit into new permissive organ site and colonize distant organs.1 The microenvironment in which the tumor originates plays an important role in tumor initiation, progression and metastasis.

KW - Adiponectin

KW - AMPK

KW - Cancer

KW - Invasion

KW - LKB1

KW - Migration

KW - S6K

UR - http://www.scopus.com/inward/record.url?scp=77956477076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956477076&partnerID=8YFLogxK

U2 - 10.4161/cam.4.3.11541

DO - 10.4161/cam.4.3.11541

M3 - Article

C2 - 20418665

AN - SCOPUS:77956477076

VL - 4

SP - 358

EP - 362

JO - Cell Adhesion and Migration

JF - Cell Adhesion and Migration

SN - 1933-6918

IS - 3

ER -