Abstract | BACKGROUND: METHODS & RESULTS: In the present study, using clinical samples (n = 88) and human PANC cell lines PANC-1, Capan-2, SW1990, and BxPC-3, we demonstrated that STIP1 is aberrantly expressed in human PANC tissues or cell lines compared to adjacent non- tumor pancreas samples or human pancreatic duct epithelial cells (HPDEC), respectively. Clinicopathological correlation studies revealed significant positive correlation between high STIP1 expression and lymph node involvement (p = 0.001), cancer metastasis (p = 0.002), microvascular invasion (p = 0.002), advance TNM stage (p = 0.024), perineural invasion (PNI; p = 0.013), and cancer-related death (p = 0.002) among patients with PANC. Univariate and multivariate analyses indicate that STIP1overexpression is an independent prognostic factor of PANC. Furthermore, STIP1 knockdown significantly inhibit the migration and invasive ability of PANC-1 and SW1990 cells, while downregulating N-cadherin and Vimentin, but upregulating E-cadherin mRNA expression levels, concurrently. We also demonstrated that STIP1 knockdown suppressed p-FAK, p-AKT, MMP2, MMP9, and Slug protein and mRNA expression levels, thus, indicating, at least in part, a role for STIP1 in the activation of FAK/AKT/ MMP signaling. CONCLUSION: Taken together, our results demonstrate a critical role for STIP1 in cancer metastasis, disease progression and poor prognosis, as well as, provide evidence suggestive of the therapeutic efficacy of STIP1-mediated targeting of the FAK/AKT/ MMP signaling axis in patients with PANC.
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Authors | Yuanming Jing, Wenqing Liang, Jian Liu, Lin Zhang, Jianguo Wei, Yafang Zhu, Jianhui Yang, Kewei Ji, Yu Zhang, Zongliang Huang |
Journal | Pathology, research and practice
(Pathol Res Pract)
Vol. 215
Issue 11
Pg. 152564
(Nov 2019)
ISSN: 1618-0631 [Electronic] Germany |
PMID | 31547977
(Publication Type: Journal Article)
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Copyright | Copyright © 2019. Published by Elsevier GmbH. |
Chemical References |
- Biomarkers, Tumor
- Heat-Shock Proteins
- STIP1 protein, human
- Focal Adhesion Kinase 1
- PTK2 protein, human
- Proto-Oncogene Proteins c-akt
- Matrix Metalloproteinases
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Topics |
- Adult
- Aged
- Biomarkers, Tumor
(analysis)
- Disease Progression
- Female
- Focal Adhesion Kinase 1
(metabolism)
- Heat-Shock Proteins
(metabolism)
- Humans
- Male
- Matrix Metalloproteinases
(metabolism)
- Middle Aged
- Pancreatic Neoplasms
(metabolism, pathology)
- Prognosis
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
(physiology)
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