SRC activates TAZ for intestinal tumorigenesis and regeneration

Mi Ran Byun, Jun Ha Hwang, A. Rum Kim, Kyung Min Kim, Jung Il Park, Ho Taek Oh, Eun Sook Hwang, Jeong-Ho Hong

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, ApcMin/+, activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalCancer Letters
Volume410
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

Regeneration
Colorectal Neoplasms
Carcinogenesis
Polyps
Proto-Oncogene Proteins
Phosphorylation
Cell Proliferation
PDZ Domains
Neoplasms
Knockout Mice
Protein-Tyrosine Kinases
Wound Healing

Keywords

  • APC
  • Colorectal cancer
  • Regeneration
  • SRC
  • TAZ

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Byun, M. R., Hwang, J. H., Kim, A. R., Kim, K. M., Park, J. I., Oh, H. T., ... Hong, J-H. (2017). SRC activates TAZ for intestinal tumorigenesis and regeneration. Cancer Letters, 410, 32-40. https://doi.org/10.1016/j.canlet.2017.09.003

SRC activates TAZ for intestinal tumorigenesis and regeneration. / Byun, Mi Ran; Hwang, Jun Ha; Kim, A. Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Hwang, Eun Sook; Hong, Jeong-Ho.

In: Cancer Letters, Vol. 410, 01.12.2017, p. 32-40.

Research output: Contribution to journalArticle

Byun, MR, Hwang, JH, Kim, AR, Kim, KM, Park, JI, Oh, HT, Hwang, ES & Hong, J-H 2017, 'SRC activates TAZ for intestinal tumorigenesis and regeneration', Cancer Letters, vol. 410, pp. 32-40. https://doi.org/10.1016/j.canlet.2017.09.003
Byun MR, Hwang JH, Kim AR, Kim KM, Park JI, Oh HT et al. SRC activates TAZ for intestinal tumorigenesis and regeneration. Cancer Letters. 2017 Dec 1;410:32-40. https://doi.org/10.1016/j.canlet.2017.09.003
Byun, Mi Ran ; Hwang, Jun Ha ; Kim, A. Rum ; Kim, Kyung Min ; Park, Jung Il ; Oh, Ho Taek ; Hwang, Eun Sook ; Hong, Jeong-Ho. / SRC activates TAZ for intestinal tumorigenesis and regeneration. In: Cancer Letters. 2017 ; Vol. 410. pp. 32-40.
@article{c097c8cf1a7e4fa48b8f90e4afb1577c,
title = "SRC activates TAZ for intestinal tumorigenesis and regeneration",
abstract = "Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, ApcMin/+, activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration.",
keywords = "APC, Colorectal cancer, Regeneration, SRC, TAZ",
author = "Byun, {Mi Ran} and Hwang, {Jun Ha} and Kim, {A. Rum} and Kim, {Kyung Min} and Park, {Jung Il} and Oh, {Ho Taek} and Hwang, {Eun Sook} and Jeong-Ho Hong",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/j.canlet.2017.09.003",
language = "English",
volume = "410",
pages = "32--40",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - SRC activates TAZ for intestinal tumorigenesis and regeneration

AU - Byun, Mi Ran

AU - Hwang, Jun Ha

AU - Kim, A. Rum

AU - Kim, Kyung Min

AU - Park, Jung Il

AU - Oh, Ho Taek

AU - Hwang, Eun Sook

AU - Hong, Jeong-Ho

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, ApcMin/+, activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration.

AB - Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, ApcMin/+, activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration.

KW - APC

KW - Colorectal cancer

KW - Regeneration

KW - SRC

KW - TAZ

UR - http://www.scopus.com/inward/record.url?scp=85030323001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030323001&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2017.09.003

DO - 10.1016/j.canlet.2017.09.003

M3 - Article

C2 - 28939028

AN - SCOPUS:85030323001

VL - 410

SP - 32

EP - 40

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

ER -