PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma
PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma
Human pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG overexpression in a representative ESCC cell line, EC9706, increased in vitro cell migration and invasion and promoted in vivo lymph node metastasis. Suppressing PTTG expression by siRNA decreased cell motility in both PTTG-HA/EC9706 and KYSE150 cells. By using mass spectrometric analysis, we identified that PTTG up-regulated S100A4 and galectin-1 secretion and down-regulated tissue inhibitor of metalloproteinase-2 secretion to the culture media. PTTG induced S100A4 and galectin-1 mRNA and protein expression as assessed by Western blot and reverse transcription-PCR. Attenuating galectin-1 expression by siRNA constrained PTTG-HA/EC9706 cell motility (P < 0.05). PTTG activated E-box transcription and induced c-Myc protein expression in EC9706 cells, which in turn may act on an E-box motif within the galectin-1 promoter. Chromatin immunoprecipitation assays further confirmed specific c-Myc binding to galectin-1 promoter. PTTG-induced galectin-1 transactivation and expression were mediated by c-Myc, and both inductions were suppressed by c-Myc RNAi cotranfection. These findings elucidate the molecular mechanisms of PTTG overexpression in promoting tumor metastasis, whereby up-regulated PTTG modulates expression and secretion of metastasis-related factors to facilitate cell motility.
PTTG, metastasis, ESCC, galectin-1, c-Myc
3283-3290
Yan, S.
590ae973-a75b-45a7-b27f-a6ad16ce7473
Zhou, C.
b01ced75-65f3-44b3-88ba-00fe9d5efb44
Lou, X.
09ff02ad-fdb2-482c-ae8d-f4b2cc210fc5
Xiao, Z.
8e37b440-0343-466f-879a-2c90a2a2e5ca
Zhu, H.
56de08ce-886f-4d04-bbc5-ee175ce014ae
Wang, Q.
55f8a112-bd52-4444-a5ba-88f920bd9a75
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Lu, N.
4717ba8c-e58e-415b-ad05-97bc323d10b4
He, S.
4e7f2b69-3d61-4c99-9e14-2f305623b5bb
Zhan, Q.
dfb5b731-5d6a-4c53-8bcc-576172c0d094
Liu, S.
3554b4ea-f13f-4ea0-af48-e7559d076cb5
Xu, N.
ea97ad95-80e3-4c01-a36c-9826718726b9
15 April 2009
Yan, S.
590ae973-a75b-45a7-b27f-a6ad16ce7473
Zhou, C.
b01ced75-65f3-44b3-88ba-00fe9d5efb44
Lou, X.
09ff02ad-fdb2-482c-ae8d-f4b2cc210fc5
Xiao, Z.
8e37b440-0343-466f-879a-2c90a2a2e5ca
Zhu, H.
56de08ce-886f-4d04-bbc5-ee175ce014ae
Wang, Q.
55f8a112-bd52-4444-a5ba-88f920bd9a75
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Lu, N.
4717ba8c-e58e-415b-ad05-97bc323d10b4
He, S.
4e7f2b69-3d61-4c99-9e14-2f305623b5bb
Zhan, Q.
dfb5b731-5d6a-4c53-8bcc-576172c0d094
Liu, S.
3554b4ea-f13f-4ea0-af48-e7559d076cb5
Xu, N.
ea97ad95-80e3-4c01-a36c-9826718726b9
Yan, S., Zhou, C., Lou, X., Xiao, Z., Zhu, H., Wang, Q., Wang, Y., Lu, N., He, S., Zhan, Q., Liu, S. and Xu, N.
(2009)
PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma.
Cancer Research, 69 (8), .
(doi:10.1158/0008-5472.CAN-08-0367).
(PMID:19351864)
Abstract
Human pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG overexpression in a representative ESCC cell line, EC9706, increased in vitro cell migration and invasion and promoted in vivo lymph node metastasis. Suppressing PTTG expression by siRNA decreased cell motility in both PTTG-HA/EC9706 and KYSE150 cells. By using mass spectrometric analysis, we identified that PTTG up-regulated S100A4 and galectin-1 secretion and down-regulated tissue inhibitor of metalloproteinase-2 secretion to the culture media. PTTG induced S100A4 and galectin-1 mRNA and protein expression as assessed by Western blot and reverse transcription-PCR. Attenuating galectin-1 expression by siRNA constrained PTTG-HA/EC9706 cell motility (P < 0.05). PTTG activated E-box transcription and induced c-Myc protein expression in EC9706 cells, which in turn may act on an E-box motif within the galectin-1 promoter. Chromatin immunoprecipitation assays further confirmed specific c-Myc binding to galectin-1 promoter. PTTG-induced galectin-1 transactivation and expression were mediated by c-Myc, and both inductions were suppressed by c-Myc RNAi cotranfection. These findings elucidate the molecular mechanisms of PTTG overexpression in promoting tumor metastasis, whereby up-regulated PTTG modulates expression and secretion of metastasis-related factors to facilitate cell motility.
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Accepted/In Press date: 11 January 2009
e-pub ahead of print date: 7 April 2009
Published date: 15 April 2009
Keywords:
PTTG, metastasis, ESCC, galectin-1, c-Myc
Organisations:
Centre for Biological Sciences
Identifiers
Local EPrints ID: 385909
URI: http://eprints.soton.ac.uk/id/eprint/385909
ISSN: 0008-5472
PURE UUID: 4c65259c-5e46-428e-8c31-af89180364a3
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Date deposited: 26 Jan 2016 10:06
Last modified: 15 Mar 2024 03:52
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Author:
S. Yan
Author:
C. Zhou
Author:
X. Lou
Author:
Z. Xiao
Author:
H. Zhu
Author:
Q. Wang
Author:
N. Lu
Author:
S. He
Author:
Q. Zhan
Author:
S. Liu
Author:
N. Xu
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