Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2022-05-20 DOI:10.3233/CBM-210435
Atsushi Murakami, T. Amano, Fumi Yoshino, H. Kita, S. Moritani, T. Murakami, T. Chano
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Abstract

BACKGROUND Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed. OBJECTIVE The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs. METHODS Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression. RESULTS Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells. CONCLUSIONS In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.
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视黄醇脱氢酶10参与卵巢透明细胞癌的癌变和细胞内碳水化合物储存。
背景:在目前的治疗方法中,卵巢透明细胞癌(OCCCs)具有复发性和难治性,因此迫切需要新的治疗方法。目的探讨RDH10作为occc治疗靶点的可行性。方法采用免疫组化方法检测RDH10在111例原发性上皮性卵巢癌中的表达,包括55例occc、31例子宫内膜样癌和25例浆液性癌。在OCCC细胞中观察RDH10引起的球状性。为了分析RDH10是否通过维生素a -糖异生途径促进碳水化合物储存,我们检测了磷酸化烯醇丙酮酸羧激酶1 (phosphoenolpyruvate carboxykinase 1, PCK1)蛋白水平和细胞内碳水化合物含量对修饰RDH10表达的响应。结果RDH10在occc中特异表达。RDH10通过调节OCCC细胞的PCK1表达促进细胞内碳水化合物的储存。结论在本研究中,丰富的RDH10参与了occc细胞的干细胞性和细胞内碳水化合物的储存。RDH10是一种潜在的治疗OCCC病例的新候选药物。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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