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Title:
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Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
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Author:
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Pérez Fusté, Noel; Castelblanco Echavarría, Esmeralda; Felip, Isidre; Santacana Espasa, Maria; Fernández-Hernández, Rita; Gatius Calderó, Sònia; Pedraza González, Neus; Pallares, Judit; Cemeli, Tània; Valls Marsal, Joan; Tarres, Marc; Ferrezuelo, Francisco; Dolcet Roca, Xavier; Matias-Guiu, Xavier; Garí Marsol, Eloi
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Notes:
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Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and
nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the
transcription of a large set of genes involved in cell cycle progress and proliferation.
However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell
migration and invasion. In this work, we have analyzed by immunohistochemistry
the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with
different types of invasion. The number of cells displaying membranous or cytoplasmic
Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective
and pushing invasion patterns of endometrial carcinoma, and in collective invasion
pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher
when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate
cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains
attached to the cell membrane therefore sequestering this cyclin in the cytoplasm.
Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic
potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1-
CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that
the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability
of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an
interesting guideline to measure cancer outcome.
This work was funded by Spanish Ministry of Education and Science (BFU2010-20293/ BMC and BFU2013-42895-P), Catalan Government (SGR-559), and Fondo de Investigaciones Sanitarias (PI10/00604 and PI13/00263). X.M-G was supported by grants 2014SGR138, RD12/0036/0013, and Fundación Asociación Española contra el Cancer. Tumour samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, and Plataforma de Biobancos ISCIII (PT13/0010/0014). NP. Fusté was supported by a contract from “Fundació Alicia Cuello de Merigó”. I. Felip and T. Cemeli were supported by a predoctoral fellowship from FPU-MINECO. |
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Subject(s):
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-Cyclin D1
-Tissue array
-Cell invasion
-Metastasis |
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Rights:
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cc-by, (c) Impact Journals, 2016
http://creativecommons.org/licenses/by/3.0/es/
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Document type:
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article
publishedVersion |
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Published by:
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Impact Journals
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Share:
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