Wnt pathway-independent activities of the APC tumor suppressor

Jenifer Prosperi, Kathleen H. Goss

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)

Abstract

The adenomatous polyposis coli (APC) tumor suppressor gene is commonly lost in both inherited and sporadic colorectal cancer and is frequently inactivated in many other human cancers. Moreover, Apc deficiency in animal models is sufficient for tumorigenesis in a diverse set of tissue types, demonstrating that APC loss not only correlates with cancer pathogenesis but drives tumor development. Over the last two decades since its identification, much attention has been devoted to deciphering the molecular mechanisms responsible for APC?s tumor suppressor activity. The picture that is emerging is one of APC as a 'gatekeeper' of epithelial and tissue homeostasis by serving as a scaffold for multi-protein complexes, including the ?-catenin destruction machinery. Although regulation of Wnt signaling by APC through ?-catenin degradation has been well studied, separable Wnt-independent functions of APC have been identified. In this review, we will summarize the interaction of APC with junctional and polarity complexes, the cytoskeleton, nuclear proteins and apoptotic factors. Emerging evidence will be presented that supports the importance of these interactions in apical-basal and front-rear polarity, migration, differentiation, DNA replication, mitosis, DNA repair and apoptosis through Wnt pathway-independent mechanisms. The contribution of these processes to tumor development as a result of APC inactivation will be discussed. Lastly, we will address how the uncoupling of these activities from Wnt signaling may provide a therapeutic opportunity for treating APC-deficient cancers. Together, these generally under-appreciated, Wnt-independent aspects of APC function may significantly revise the accepted view of APC-mediated tumor suppression and, importantly, uncover novel strategies for cancer treatment.

Original languageEnglish (US)
Title of host publicationTumor Suppressors
PublisherNova Science Publishers, Inc.
Pages105-132
Number of pages28
ISBN (Print)9781617619861
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Wnt Signaling Pathway
Adenomatous Polyposis Coli
Tumors
Catenins
Neoplasms
Tissue homeostasis
Oncology
DNA
Nuclear Proteins
Scaffolds
Machinery
Animals
Repair
Genes
Tissue
Apoptosis
Degradation
Tumor Suppressor Genes
Cytoskeleton
DNA Replication

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Prosperi, J., & Goss, K. H. (2011). Wnt pathway-independent activities of the APC tumor suppressor. In Tumor Suppressors (pp. 105-132). Nova Science Publishers, Inc..

Wnt pathway-independent activities of the APC tumor suppressor. / Prosperi, Jenifer; Goss, Kathleen H.

Tumor Suppressors. Nova Science Publishers, Inc., 2011. p. 105-132.

Research output: Chapter in Book/Report/Conference proceedingChapter

Prosperi, J & Goss, KH 2011, Wnt pathway-independent activities of the APC tumor suppressor. in Tumor Suppressors. Nova Science Publishers, Inc., pp. 105-132.
Prosperi J, Goss KH. Wnt pathway-independent activities of the APC tumor suppressor. In Tumor Suppressors. Nova Science Publishers, Inc. 2011. p. 105-132
Prosperi, Jenifer ; Goss, Kathleen H. / Wnt pathway-independent activities of the APC tumor suppressor. Tumor Suppressors. Nova Science Publishers, Inc., 2011. pp. 105-132
@inbook{d9dff3d93f594bec8952938ba6324344,
title = "Wnt pathway-independent activities of the APC tumor suppressor",
abstract = "The adenomatous polyposis coli (APC) tumor suppressor gene is commonly lost in both inherited and sporadic colorectal cancer and is frequently inactivated in many other human cancers. Moreover, Apc deficiency in animal models is sufficient for tumorigenesis in a diverse set of tissue types, demonstrating that APC loss not only correlates with cancer pathogenesis but drives tumor development. Over the last two decades since its identification, much attention has been devoted to deciphering the molecular mechanisms responsible for APC?s tumor suppressor activity. The picture that is emerging is one of APC as a 'gatekeeper' of epithelial and tissue homeostasis by serving as a scaffold for multi-protein complexes, including the ?-catenin destruction machinery. Although regulation of Wnt signaling by APC through ?-catenin degradation has been well studied, separable Wnt-independent functions of APC have been identified. In this review, we will summarize the interaction of APC with junctional and polarity complexes, the cytoskeleton, nuclear proteins and apoptotic factors. Emerging evidence will be presented that supports the importance of these interactions in apical-basal and front-rear polarity, migration, differentiation, DNA replication, mitosis, DNA repair and apoptosis through Wnt pathway-independent mechanisms. The contribution of these processes to tumor development as a result of APC inactivation will be discussed. Lastly, we will address how the uncoupling of these activities from Wnt signaling may provide a therapeutic opportunity for treating APC-deficient cancers. Together, these generally under-appreciated, Wnt-independent aspects of APC function may significantly revise the accepted view of APC-mediated tumor suppression and, importantly, uncover novel strategies for cancer treatment.",
author = "Jenifer Prosperi and Goss, {Kathleen H.}",
year = "2011",
month = "1",
language = "English (US)",
isbn = "9781617619861",
pages = "105--132",
booktitle = "Tumor Suppressors",
publisher = "Nova Science Publishers, Inc.",

}

TY - CHAP

T1 - Wnt pathway-independent activities of the APC tumor suppressor

AU - Prosperi, Jenifer

AU - Goss, Kathleen H.

PY - 2011/1

Y1 - 2011/1

N2 - The adenomatous polyposis coli (APC) tumor suppressor gene is commonly lost in both inherited and sporadic colorectal cancer and is frequently inactivated in many other human cancers. Moreover, Apc deficiency in animal models is sufficient for tumorigenesis in a diverse set of tissue types, demonstrating that APC loss not only correlates with cancer pathogenesis but drives tumor development. Over the last two decades since its identification, much attention has been devoted to deciphering the molecular mechanisms responsible for APC?s tumor suppressor activity. The picture that is emerging is one of APC as a 'gatekeeper' of epithelial and tissue homeostasis by serving as a scaffold for multi-protein complexes, including the ?-catenin destruction machinery. Although regulation of Wnt signaling by APC through ?-catenin degradation has been well studied, separable Wnt-independent functions of APC have been identified. In this review, we will summarize the interaction of APC with junctional and polarity complexes, the cytoskeleton, nuclear proteins and apoptotic factors. Emerging evidence will be presented that supports the importance of these interactions in apical-basal and front-rear polarity, migration, differentiation, DNA replication, mitosis, DNA repair and apoptosis through Wnt pathway-independent mechanisms. The contribution of these processes to tumor development as a result of APC inactivation will be discussed. Lastly, we will address how the uncoupling of these activities from Wnt signaling may provide a therapeutic opportunity for treating APC-deficient cancers. Together, these generally under-appreciated, Wnt-independent aspects of APC function may significantly revise the accepted view of APC-mediated tumor suppression and, importantly, uncover novel strategies for cancer treatment.

AB - The adenomatous polyposis coli (APC) tumor suppressor gene is commonly lost in both inherited and sporadic colorectal cancer and is frequently inactivated in many other human cancers. Moreover, Apc deficiency in animal models is sufficient for tumorigenesis in a diverse set of tissue types, demonstrating that APC loss not only correlates with cancer pathogenesis but drives tumor development. Over the last two decades since its identification, much attention has been devoted to deciphering the molecular mechanisms responsible for APC?s tumor suppressor activity. The picture that is emerging is one of APC as a 'gatekeeper' of epithelial and tissue homeostasis by serving as a scaffold for multi-protein complexes, including the ?-catenin destruction machinery. Although regulation of Wnt signaling by APC through ?-catenin degradation has been well studied, separable Wnt-independent functions of APC have been identified. In this review, we will summarize the interaction of APC with junctional and polarity complexes, the cytoskeleton, nuclear proteins and apoptotic factors. Emerging evidence will be presented that supports the importance of these interactions in apical-basal and front-rear polarity, migration, differentiation, DNA replication, mitosis, DNA repair and apoptosis through Wnt pathway-independent mechanisms. The contribution of these processes to tumor development as a result of APC inactivation will be discussed. Lastly, we will address how the uncoupling of these activities from Wnt signaling may provide a therapeutic opportunity for treating APC-deficient cancers. Together, these generally under-appreciated, Wnt-independent aspects of APC function may significantly revise the accepted view of APC-mediated tumor suppression and, importantly, uncover novel strategies for cancer treatment.

UR - http://www.scopus.com/inward/record.url?scp=82455190746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82455190746&partnerID=8YFLogxK

M3 - Chapter

AN - SCOPUS:82455190746

SN - 9781617619861

SP - 105

EP - 132

BT - Tumor Suppressors

PB - Nova Science Publishers, Inc.

ER -