PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma - PubMed (original) (raw)

. 2009 Apr 15;69(8):3283-90.

doi: 10.1158/0008-5472.CAN-08-0367. Epub 2009 Apr 7.

Cuiqi Zhou, Xiaomin Lou, Zefen Xiao, Hongxia Zhu, Qifeng Wang, Yihua Wang, Ning Lu, Shun He, Qimin Zhan, Siqi Liu, Ningzhi Xu

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PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma

Shuang Yan et al. Cancer Res. 2009.

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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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