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Functional characterization of a candidate tumor suppressor gene, Mirror Image Polydactyly 1, in nasopharyngeal carcinoma.
Functional characterization of a candidate tumor suppressor gene, Mirror Image Polydactyly 1, in nasopharyngeal carcinoma.
- Source :
-
International journal of cancer [Int J Cancer] 2020 May 15; Vol. 146 (10), pp. 2891-2900. Date of Electronic Publication: 2019 Nov 01. - Publication Year :
- 2020
-
Abstract
- Mirror Image Polydactyly 1 (MIPOL1) is generally associated with congenital anomalies. However, its role in cancer development is poorly understood. Previously, by utilizing the functional complementation approach, microcell-mediated chromosome transfer (MMCT), a tumor suppressor gene, MIPOL1, was identified. MIPOL1 was confirmed to be downregulated in nasopharyngeal carcinoma (NPC) cells and tumor tissues, and re-expression of MIPOL1 induced tumor suppression. The aim of the current study is to further elucidate the functional tumor suppressive role of MIPOL1. In our study, with an expanded sample size of different clinical stages of NPC tumor tissues, we further confirmed the downregulation of MIPOL1 in different cancer stages. MIPOL1 re-expression down-regulated angiogenic factors and reduced phosphorylation of metastasis-associated proteins including AKT, p65, and FAK. In addition, MIPOL1 was confirmed to interact with a tumor suppressor, RhoB, and re-expression of MIPOL1 enhanced RhoB activity. The functional role of MIPOL1 was further validated by utilizing a panel of wild-type (WT) and truncated MIPOL1 expression constructs. The MIPOL1 tumor-suppressive effect can only be observed in the WT MIPOL1-expressing cells. In vitro and nude mice in vivo functional studies further confirmed the critical role of WT MIPOL1 in inhibiting migration, invasion and metastasis in NPC. Overall, our study provides strong evidence about the tumor-suppressive role of MIPOL1 in inhibiting angiogenesis and metastasis in NPC.<br /> (© 2019 UICC.)
- Subjects :
- Animals
Heterografts
Humans
Mice
Mice, Nude
Nasopharyngeal Carcinoma metabolism
Nasopharyngeal Carcinoma pathology
Nasopharyngeal Neoplasms metabolism
Nasopharyngeal Neoplasms pathology
Gene Expression Regulation, Neoplastic physiology
Genes, Tumor Suppressor physiology
Nasopharyngeal Carcinoma genetics
Nasopharyngeal Neoplasms genetics
Tumor Suppressor Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 146
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31609475
- Full Text :
- https://doi.org/10.1002/ijc.32732