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Int. J. Mol. Sci. 2017, 18(6), 1251; doi:10.3390/ijms18061251

AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors

1
Biosanitary Research Institute, ibs.Granada, 18012 Granada, Spain
2
Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, 18012 Granada, Spain
3
Department of Radiology and Physical Medicine, University of Granada, 18012 Granada, Spain
4
General Surgery Unit, San Cecilio University Hospital, 18012 Granada, Spain
5
Ciber of Hepatic and Digestive Diseases (CIBERehd), Biosanitary Research Institute, ibs.Granada, 18012 Granada, Spain
6
Pediatric Unit, Granada University and San Cecilio University Hospital, 18012 Granada, Spain
These authors contribute equally to this work.
*
Author to whom correspondence should be addressed.
Received: 17 March 2017 / Revised: 5 June 2017 / Accepted: 7 June 2017 / Published: 11 June 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
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Abstract

The characterization of colon cancer stem cells (CSCs) may help to develop novel diagnostic and therapeutic procedures. p53 loss increases the pool of CSCs in colorectal cancer (CRC). Recent reports suggest that the oncostatic effects of melatonin could be related to its ability to kill CSCs. Although there are no data linking the loss of p53 function and melatonin synthesis or signaling in cancer, melatonin does activate the p53 tumor-suppressor pathway in this disease. In this work, we analyze whether the expression of melatonin synthesis and signaling genes are related to the expression of CSC markers and the implication of p53 status in samples from patients with CRC. Arylalkylamine N-acetyltransferase (AA-NAT), MT1, and MT2 expression decreased in tumor samples versus normal mucosa samples in mutated p53 (mtp53) tumors versus those with wild-type p53 (wtp53). Further, AA-NAT and MT2 expression were lower in advanced stages of the disease in wtp53 tumors. On the contrary, CD44 and CD66c expression was higher in tumor versus normal mucosa in wtp53 tumors. Additionally, CD44 expression was higher in advanced stages of the disease regardless of the p53 status. Patients with CD44highCD66chigh and wtp53 tumors in advanced stages showed low expression of AA-NAT and MT2 in wtp53 tumors. These results could indicate a possible interaction of these pathways in CRC. View Full-Text
Keywords: colorectal cancer; melatonin; cancer stem cells; p53; metastasis colorectal cancer; melatonin; cancer stem cells; p53; metastasis
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Casado, J.; Iñigo-Chaves, A.; Jiménez-Ruiz, S.M.; Ríos-Arrabal, S.; Carazo-Gallego, Á.; González-Puga, C.; Núñez, M.I.; Ruíz-Extremera, Á.; Salmerón, J.; León, J. AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors. Int. J. Mol. Sci. 2017, 18, 1251.

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