IAP Regulation of Metastasis

Swarna Mehrotra; Lucia R. Languino; Christopher M. Raskett; Arthur M. Mercurio; Takehiko Dohi; Dario C. Altieri

doi:10.1016/j.ccr.2009.11.021

IAP Regulation of Metastasis

Swarna Mehrotra
, Lucia R. Languino
, Christopher M. Raskett
, Arthur M. Mercurio
, Takehiko Dohi
, Dario C. Altieri

Department of Surgery

Research output: Contribution to journal › Article › peer-review

253 Scopus citations

Abstract

Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.

Original language	English (US)
Pages (from-to)	53-64
Number of pages	12
Journal	Cancer Cell
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2009.11.021
State	Published - Jan 19 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Oncology
Cell Biology
Cancer Research

Access to Document

10.1016/j.ccr.2009.11.021

Cite this

@article{7d17ecc47e364ddea7568202a5627a3b,

title = "IAP Regulation of Metastasis",

abstract = "Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.",

author = "Swarna Mehrotra and Languino, \{Lucia R.\} and Raskett, \{Christopher M.\} and Mercurio, \{Arthur M.\} and Takehiko Dohi and Altieri, \{Dario C.\}",

note = "Funding Information: We thank Leslie Shaw for discussion, I.-S. Kim for a fibronectin promoter reporter construct, Michelle Kelliher for FSIPPW vector, Bert Vogelstein for HCT116 cells, Colin Duckett for XIAP −/− mouse embryonic fibroblasts and D148A/W310A XIAP cDNA, and Robert Sherwin for INS-1 cells. This work was supported by National Institutes of Health grants CA89720 (to L.R.L.); CA107548 (to A.M.M.); and CA78810, CA90917, CA118005, and HL54131 (to D.C.A.). ",

year = "2010",

month = jan,

day = "19",

doi = "10.1016/j.ccr.2009.11.021",

language = "English (US)",

volume = "17",

pages = "53--64",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - IAP Regulation of Metastasis

AU - Mehrotra, Swarna

AU - Languino, Lucia R.

AU - Raskett, Christopher M.

AU - Mercurio, Arthur M.

AU - Dohi, Takehiko

AU - Altieri, Dario C.

N1 - Funding Information: We thank Leslie Shaw for discussion, I.-S. Kim for a fibronectin promoter reporter construct, Michelle Kelliher for FSIPPW vector, Bert Vogelstein for HCT116 cells, Colin Duckett for XIAP −/− mouse embryonic fibroblasts and D148A/W310A XIAP cDNA, and Robert Sherwin for INS-1 cells. This work was supported by National Institutes of Health grants CA89720 (to L.R.L.); CA107548 (to A.M.M.); and CA78810, CA90917, CA118005, and HL54131 (to D.C.A.).

PY - 2010/1/19

Y1 - 2010/1/19

N2 - Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.

AB - Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.

UR - https://www.scopus.com/pages/publications/73649095563

UR - https://www.scopus.com/pages/publications/73649095563#tab=citedBy

U2 - 10.1016/j.ccr.2009.11.021

DO - 10.1016/j.ccr.2009.11.021

M3 - Article

C2 - 20129247

AN - SCOPUS:73649095563

SN - 1535-6108

VL - 17

SP - 53

EP - 64

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

IAP Regulation of Metastasis

Abstract

UN SDGs

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this