Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis

Yi Tang; Varalakshmi Katuri; Radhika Srinivasan; Franz Fogt; Robert Redman; Girish Anand; Anan Said; Thomas Fishbein; Michael Zasloff; E. Premkumar Reddy; Bibhuti Mishra; Lopa Mishra

doi:10.1158/0008-5472.CAN-04-4585

Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis

Yi Tang, Varalakshmi Katuri, Radhika Srinivasan, Franz Fogt, Robert Redman, Girish Anand, Anan Said, Thomas Fishbein, Michael Zasloff, E. Premkumar Reddy, Bibhuti Mishra, Lopa Mishra

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

81 Scopus citations

Abstract

Although transforming growth factor-β (TGF-β) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a β-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-β to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf ^+/-/Smad4^+/-, elf^+/-, Smad4^+/-, and gut epithelial cells from elf^-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-β signaling in the suppression of early colon cancer.

Original language	English
Pages (from-to)	4228-4237
Number of pages	10
Journal	Cancer Research
Volume	65
Issue number	10
DOIs	https://doi.org/10.1158/0008-5472.CAN-04-4585
State	Published - 15 May 2005
Externally published	Yes

Access to Document

10.1158/0008-5472.CAN-04-4585

Cite this

Tang, Y., Katuri, V., Srinivasan, R., Fogt, F., Redman, R., Anand, G., Said, A., Fishbein, T., Zasloff, M., Reddy, E. P., Mishra, B., & Mishra, L. (2005). Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis. Cancer Research, 65(10), 4228-4237. https://doi.org/10.1158/0008-5472.CAN-04-4585

@article{161ba5f0f66849b9af4b4869558ff944,

title = "Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis",

abstract = "Although transforming growth factor-β (TGF-β) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a β-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-β to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf +/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-β signaling in the suppression of early colon cancer.",

author = "Yi Tang and Varalakshmi Katuri and Radhika Srinivasan and Franz Fogt and Robert Redman and Girish Anand and Anan Said and Thomas Fishbein and Michael Zasloff and Reddy, {E. Premkumar} and Bibhuti Mishra and Lopa Mishra",

year = "2005",

month = may,

day = "15",

doi = "10.1158/0008-5472.CAN-04-4585",

language = "English",

volume = "65",

pages = "4228--4237",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "10",

}

Tang, Y, Katuri, V, Srinivasan, R, Fogt, F, Redman, R, Anand, G, Said, A, Fishbein, T, Zasloff, M, Reddy, EP, Mishra, B & Mishra, L 2005, 'Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis', Cancer Research, vol. 65, no. 10, pp. 4228-4237. https://doi.org/10.1158/0008-5472.CAN-04-4585

TY - JOUR

T1 - Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis

AU - Tang, Yi

AU - Katuri, Varalakshmi

AU - Srinivasan, Radhika

AU - Fogt, Franz

AU - Redman, Robert

AU - Anand, Girish

AU - Said, Anan

AU - Fishbein, Thomas

AU - Zasloff, Michael

AU - Reddy, E. Premkumar

AU - Mishra, Bibhuti

AU - Mishra, Lopa

PY - 2005/5/15

Y1 - 2005/5/15

N2 - Although transforming growth factor-β (TGF-β) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a β-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-β to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf +/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-β signaling in the suppression of early colon cancer.

AB - Although transforming growth factor-β (TGF-β) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a β-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-β to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf +/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-β signaling in the suppression of early colon cancer.

UR - http://www.scopus.com/inward/record.url?scp=20144378766&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-4585

DO - 10.1158/0008-5472.CAN-04-4585

M3 - Article

C2 - 15899814

AN - SCOPUS:20144378766

SN - 0008-5472

VL - 65

SP - 4228

EP - 4237

JO - Cancer Research

JF - Cancer Research

IS - 10

ER -

Transforming growth factor-β suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis

Abstract

Access to Document

Fingerprint

Cite this