Mansour, M. A. and Senga, T. (2017) HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer. International Journal of Biochemistry and Cell Biology, 88, pp. 1-13. (doi: 10.1016/j.biocel.2017.04.011) (PMID:28457970)
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Abstract
Homeobox (HOX) genes are conserved transcription factors which determine the anterior-posterior body axis patterning. HOXD8 is a member of HOX genes deregulated in several tumors such as lung carcinoma, neuroblastoma, glioma and colorectal cancer (CRC) in a context-dependent manner. In CRC, HOXD8 is downregulated in cancer tissues and metastatic foci as compared to normal tissues. Whether HOXD8 acts as a tumor suppressor of malignant progression and metastasis is still unclear. Also, the underlying mechanism of its function including the downstream targets is totally unknown. Here, we clarified the lower expression of HOXD8 in clinical colorectal cancer vs. normal colon tissues. Also, we showed that stable expression of HOXD8 in colorectal cancer cells significantly reduced the cell proliferation, anchorage-independent growth and invasion. Further, using The Cancer Genome Atlas (TCGA), we identified the genes associated with HOXD8 in order to demonstrate its function as a suppressor or a promoter of colorectal carcinoma. Among inversely related genes, apoptotic inhibitors like STK38 kinase and MYC were shown to be negatively associated with HOXD8. We demonstrated the ability of HOXD8 to upregulate executioner caspases 6 & 7 and cleaved PARP, thus inducing the apoptotic events in colorectal cancer cells.
| Item Type: | Articles |
|---|---|
| Keywords: | Apoptosis, colorectal cancer, HOXD8, homology modeling, MYC, STK38, TCGA. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Mansour, Dr Mohammed Ahmed |
| Authors: | Mansour, M. A., and Senga, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | International Journal of Biochemistry and Cell Biology |
| Publisher: | Elsevier |
| ISSN: | 1357-2725 |
| ISSN (Online): | 1878-5875 |
| Published Online: | 27 April 2017 |
| Copyright Holders: | Copyright © 2017 Elsevier Ltd. |
| First Published: | First published in International Journal of Biochemistry and Cell Biology 88: 1-13 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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