Your browser doesn't support javascript.
loading
EFHD1 promotes osteosarcoma proliferation and drug resistance by inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP) by binding to ANT3.
Shen, Xin; Ma, Mengjun; Mi, Rujia; Zhuang, Jiahao; Song, Yihui; Yang, Wen; Li, Hongyu; Lu, Yixuan; Yang, Biao; Liu, Yinliang; Wu, Yanfeng; Shen, Huiyong.
Afiliação
  • Shen X; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Ma M; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Mi R; Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Zhuang J; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Song Y; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Yang W; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Li H; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Lu Y; Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Yang B; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Liu Y; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China.
  • Wu Y; Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China. wuyf@mail.sysu.edu.cn.
  • Shen H; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Zhong Road, Shenzhen, 518033, Guangdong, China. shenhuiy@mail.sysu.edu.cn.
Cell Mol Life Sci ; 81(1): 236, 2024 May 25.
Article em En | MEDLINE | ID: mdl-38795203
ABSTRACT
Chemoresistance is the main obstacle in the clinical treatment of osteosarcoma (OS). In this study, we investigated the role of EF-hand domain-containing protein 1 (EFHD1) in OS chemotherapy resistance. We found that the expression of EFHD1 was highly correlated with the clinical outcome after chemotherapy. We overexpressed EFHD1 in 143B cells and found that it increased their resistance to cell death after drug treatment. Conversely, knockdown of EFHD1 in 143BR cells (a cisplatin-less-sensitive OS cell line derived from 143B cells) increased their sensitivity to treatment. Mechanistically, EFHD1 bound to adenine nucleotide translocase-3 (ANT3) and inhibited its conformational change, thereby inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP). This effect could maintain mitochondrial function, thereby favoring OS cell survival. The ANT3 conformational inhibitor carboxyatractyloside (CATR), which can promote mPTP opening, enhanced the chemosensitivity of EFHD1-overexpressing cells when combined with cisplatin. The ANT3 conformational inhibitor bongkrekic acid (BKA), which can inhibit mPTP opening, restored the resistance of EFHD1 knockdown cells. In conclusion, our results suggest that EFHD1-ANT3-mPTP might be a promising target for OS therapy in the future.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteossarcoma / Cisplatino / Resistencia a Medicamentos Antineoplásicos / Proteínas de Transporte da Membrana Mitocondrial / Proliferação de Células / Poro de Transição de Permeabilidade Mitocondrial Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteossarcoma / Cisplatino / Resistencia a Medicamentos Antineoplásicos / Proteínas de Transporte da Membrana Mitocondrial / Proliferação de Células / Poro de Transição de Permeabilidade Mitocondrial Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article