Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma

被引：11

作者：

Chan, Nyein Nyein ^{[1
,2
,3
]}

Yamazaki, Manabu ^{[1
,2
]}

Maruyama, Satoshi ^{[4
]}

Abe, Tatsuya ^{[1
,2
]}

Haga, Kenta ^{[2
,3
]}

Kawaharada, Masami ^{[2
,3
]}

Izumi, Kenji ^{[2
,5
]}

Kobayashi, Tadaharu ^{[2
,3
]}

Tanuma, Jun-ichi ^{[1
,2
,4
]}

机构：

[1] Niigata Univ, Div Oral Pathol, Dept Tissue Regenerat & Reconstruct, Fac Dent, Niigata 9518514, Japan

[2] Niigata Univ, Grad Sch Med & Dent Sci, Niigata 9518514, Japan

[3] Niigata Univ, Fac Dent, Div Reconstruct Surg Oral & Maxillofacial Reg, Niigata 9518514, Japan

[4] Niigata Univ Hosp, Dept Surg Pathol, Oral Pathol Sect, Niigata 9518520, Japan

[5] Niigata Univ, Fac Dent, Div Biomimetics, Dept Oral Hlth Sci, Niigata 9518514, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 07期

基金：

日本学术振兴会;

关键词：

caveolin-1; cell polarization; cholesterol; migration; oral squamous cell carcinoma; SERUM-LIPID PROFILE; CAVEOLIN-1; EXPRESSION; POLARIZATION; CANCER; PROTEIN; ACTIN; DOMAINS; EDGE;

D O I：

10.3390/ijms24076035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta-cyclodextrin and increased using the methyl-beta-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.

引用

页数：18

共 65 条

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