AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts

Jing Zhang, Serkin Park, Marlene C. Artime, Justin M. Summy, Ami N. Shah, Joshua A. Bomser, Andrea Dorfleutner, Daniel C. Flynn, Gary E. Gallick

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC. Here we investigated the roles of AFAP-110 in the tumorigenic process of prostate carcinoma. Using immunohistochemistry of human tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia but significantly increased in prostate carcinomas. The level of AFAP-110 in carcinomas correlated with the Gleason scores. Downregulation of AFAP-110 in PC3 prostate cancer cells inhibited cell proliferation in vitro and tumorigenicity and growth in orthotopic nude mouse models. Furthermore, downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin β1 expression. Reintroduction of avian AFAP-110 or a mutant disabling its interaction with Src restored these properties. However, expression of an AFAP-110 lacking the PKC-interacting domain failed to restore properties of parental cells. Thus, increased expression of AFAP-110 is associated with progressive stages of prostate cancer and is critical for tumorigenic growth, in part by regulating focal contacts in a PKC-dependent mechanism.

Original languageEnglish
Pages (from-to)2962-2973
Number of pages12
JournalJournal of Clinical Investigation
Volume117
Issue number10
DOIs
Publication statusPublished - 2007 Oct 1
Externally publishedYes

Fingerprint

Focal Adhesions
Prostatic Neoplasms
Growth
Carcinoma
Actin Cytoskeleton
Prostate
src Genes
AFAP 110
Cell-Matrix Junctions
Proteins
Neoplasm Grading
Prostatic Hyperplasia
Nude Mice
Integrins
Cell Movement
Actins
Down-Regulation
Epithelium
Immunohistochemistry
Cell Proliferation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts. / Zhang, Jing; Park, Serkin; Artime, Marlene C.; Summy, Justin M.; Shah, Ami N.; Bomser, Joshua A.; Dorfleutner, Andrea; Flynn, Daniel C.; Gallick, Gary E.

In: Journal of Clinical Investigation, Vol. 117, No. 10, 01.10.2007, p. 2962-2973.

Research output: Contribution to journalArticle

Zhang, J, Park, S, Artime, MC, Summy, JM, Shah, AN, Bomser, JA, Dorfleutner, A, Flynn, DC & Gallick, GE 2007, 'AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts', Journal of Clinical Investigation, vol. 117, no. 10, pp. 2962-2973. https://doi.org/10.1172/JCI30710
Zhang, Jing ; Park, Serkin ; Artime, Marlene C. ; Summy, Justin M. ; Shah, Ami N. ; Bomser, Joshua A. ; Dorfleutner, Andrea ; Flynn, Daniel C. ; Gallick, Gary E. / AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 10. pp. 2962-2973.
@article{9bca1bfc8f9e4b4b91f2244fc33bd24d,
title = "AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts",
abstract = "The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC. Here we investigated the roles of AFAP-110 in the tumorigenic process of prostate carcinoma. Using immunohistochemistry of human tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia but significantly increased in prostate carcinomas. The level of AFAP-110 in carcinomas correlated with the Gleason scores. Downregulation of AFAP-110 in PC3 prostate cancer cells inhibited cell proliferation in vitro and tumorigenicity and growth in orthotopic nude mouse models. Furthermore, downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin β1 expression. Reintroduction of avian AFAP-110 or a mutant disabling its interaction with Src restored these properties. However, expression of an AFAP-110 lacking the PKC-interacting domain failed to restore properties of parental cells. Thus, increased expression of AFAP-110 is associated with progressive stages of prostate cancer and is critical for tumorigenic growth, in part by regulating focal contacts in a PKC-dependent mechanism.",
author = "Jing Zhang and Serkin Park and Artime, {Marlene C.} and Summy, {Justin M.} and Shah, {Ami N.} and Bomser, {Joshua A.} and Andrea Dorfleutner and Flynn, {Daniel C.} and Gallick, {Gary E.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1172/JCI30710",
language = "English",
volume = "117",
pages = "2962--2973",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

TY - JOUR

T1 - AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts

AU - Zhang, Jing

AU - Park, Serkin

AU - Artime, Marlene C.

AU - Summy, Justin M.

AU - Shah, Ami N.

AU - Bomser, Joshua A.

AU - Dorfleutner, Andrea

AU - Flynn, Daniel C.

AU - Gallick, Gary E.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC. Here we investigated the roles of AFAP-110 in the tumorigenic process of prostate carcinoma. Using immunohistochemistry of human tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia but significantly increased in prostate carcinomas. The level of AFAP-110 in carcinomas correlated with the Gleason scores. Downregulation of AFAP-110 in PC3 prostate cancer cells inhibited cell proliferation in vitro and tumorigenicity and growth in orthotopic nude mouse models. Furthermore, downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin β1 expression. Reintroduction of avian AFAP-110 or a mutant disabling its interaction with Src restored these properties. However, expression of an AFAP-110 lacking the PKC-interacting domain failed to restore properties of parental cells. Thus, increased expression of AFAP-110 is associated with progressive stages of prostate cancer and is critical for tumorigenic growth, in part by regulating focal contacts in a PKC-dependent mechanism.

AB - The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC. Here we investigated the roles of AFAP-110 in the tumorigenic process of prostate carcinoma. Using immunohistochemistry of human tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia but significantly increased in prostate carcinomas. The level of AFAP-110 in carcinomas correlated with the Gleason scores. Downregulation of AFAP-110 in PC3 prostate cancer cells inhibited cell proliferation in vitro and tumorigenicity and growth in orthotopic nude mouse models. Furthermore, downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin β1 expression. Reintroduction of avian AFAP-110 or a mutant disabling its interaction with Src restored these properties. However, expression of an AFAP-110 lacking the PKC-interacting domain failed to restore properties of parental cells. Thus, increased expression of AFAP-110 is associated with progressive stages of prostate cancer and is critical for tumorigenic growth, in part by regulating focal contacts in a PKC-dependent mechanism.

UR - http://www.scopus.com/inward/record.url?scp=34948910770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34948910770&partnerID=8YFLogxK

U2 - 10.1172/JCI30710

DO - 10.1172/JCI30710

M3 - Article

C2 - 17885682

AN - SCOPUS:34948910770

VL - 117

SP - 2962

EP - 2973

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 10

ER -