Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma
Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. Howe...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6035 |
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| author | Nyein Nyein Chan Manabu Yamazaki Satoshi Maruyama Tatsuya Abé Kenta Haga Masami Kawaharada Kenji Izumi Tadaharu Kobayashi Jun-ichi Tanuma |
| author_facet | Nyein Nyein Chan Manabu Yamazaki Satoshi Maruyama Tatsuya Abé Kenta Haga Masami Kawaharada Kenji Izumi Tadaharu Kobayashi Jun-ichi Tanuma |
| author_sort | Nyein Nyein Chan |
| collection | DOAJ |
| description | Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-β-cyclodextrin and increased using the methyl-β-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients. |
| first_indexed | 2024-03-11T05:36:52Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:52Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6bc35fad1a814ffc9dec3a4d06b6e8a82023-11-17T16:45:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247603510.3390/ijms24076035Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell CarcinomaNyein Nyein Chan0Manabu Yamazaki1Satoshi Maruyama2Tatsuya Abé3Kenta Haga4Masami Kawaharada5Kenji Izumi6Tadaharu Kobayashi7Jun-ichi Tanuma8Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanOral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, JapanDivision of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Biomimetics, Department of Oral Health Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanDivision of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, JapanCholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-β-cyclodextrin and increased using the methyl-β-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.https://www.mdpi.com/1422-0067/24/7/6035caveolin-1cell polarizationcholesterolmigrationoral squamous cell carcinoma |
| spellingShingle | Nyein Nyein Chan Manabu Yamazaki Satoshi Maruyama Tatsuya Abé Kenta Haga Masami Kawaharada Kenji Izumi Tadaharu Kobayashi Jun-ichi Tanuma Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma International Journal of Molecular Sciences caveolin-1 cell polarization cholesterol migration oral squamous cell carcinoma |
| title | Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma |
| title_full | Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma |
| title_fullStr | Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma |
| title_short | Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma |
| title_sort | cholesterol is a regulator of cav1 localization and cell migration in oral squamous cell carcinoma |
| topic | caveolin-1 cell polarization cholesterol migration oral squamous cell carcinoma |
| url | https://www.mdpi.com/1422-0067/24/7/6035 |
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