Abnormal accumulation of OFD1 in endometrial cancer with poor prognosis inhibits ciliogenesis

Kojima,Ryuji; Kojima,Ryuji; Hassan,Esraa; Hassan,Esraa; Ozawa,Fumiko; Ozawa,Fumiko; Yamada‑Namikawa,Chisato; Yamada‑Namikawa,Chisato; Ogawa,Shino; Ogawa,Shino; Mase,Shoko; Mase,Shoko; Goto,Shinobu; Goto,Shinobu; Nishikawa,Ryutaro; Nishikawa,Ryutaro; Inagaki,Hiroshi; Inagaki,Hiroshi; Kato,Yoichi; Kato,Yoichi; Sugiura‑Ogasawara,Mayumi; Sugiura‑Ogasawara,Mayumi

doi:10.3892/ol.2022.13334

Abnormal accumulation of OFD1 in endometrial cancer with poor prognosis inhibits ciliogenesis

Authors:
- Ryuji Kojima
- Esraa Hassan
- Fumiko Ozawa
- Chisato Yamada‑Namikawa
- Shino Ogawa
- Shoko Mase
- Shinobu Goto
- Ryutaro Nishikawa
- Hiroshi Inagaki
- Yoichi Kato
- Mayumi Sugiura‑Ogasawara
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Affiliations: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Cell Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan
Published online on: May 17, 2022 https://doi.org/10.3892/ol.2022.13334
Article Number: 214
Copyright: © Kojima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to examine primary cilia in endometrial tissue during the menstrual cycle and to clarify their morphological changes with different grades of endometrial cancer. Images of fluorescence immunostaining taken by confocal microscopy were used to count the number of primary cilia in normal endometrium and endometrioid carcinoma Grade 1 and Grade 3 specimens. To examine the association between autophagy and ciliogenesis in endometrioid carcinoma, the expression of p62/Sequestosome‑1, a selective substrate for autophagy, and oral‑facial‑digital syndrome 1 protein (OFD1), a protein associated with ciliogenesis, were examined using images of fluorescence immunostaining taken by confocal microscopy. The level of p62 expression was confirmed by western blotting. In proliferative and secretory endometrial stromal cells, the percentage of cells that were ciliated was 7.2 and 32.7% (95% confidence interval=21.61‑39.79; P<0.01), and the length of the primary cilia was 1.24 µm and 2.34 µm (0.92‑1.26; P<0.01), respectively. In stromal cells of endometrioid carcinoma Grade 1 and Grade 3, the percentage of ciliated cells was 13.5 and 2.9% (7.89‑15.05; P<0.001), and the length of the primary cilia was 2.02 and 1.14 µm (0.76‑0.99; P<0.001), respectively. In both normal menstrual cycle tissue and endometrial carcinomas, the percentage of primary cilia was lower and their length was shorter in tissues with higher proliferative potential. The expression of OFD1 was significantly higher in Grade 3 compared with Grade 1 as indicated by quantifying the intensity of the fluorescence images (133‑12248; P=0.046). To the best of our knowledge, this is the first study concerning the distribution of primary cilia in normal endometrium and endometrial cancer tissues. Overall, fewer ciliated cells in the highly malignant endometrial cancer tissues may be associated not only to the proliferation of cancer cells, but also to the excessive accumulation of OFD1 due to dysfunctional autophagy.

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