The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway

Wang, Fuhao1,2; Fu, Xing1; Chang, Ming1; Wei, Tianzi1; Lin, Risheng1; Tong, Haibo3; Zhang, Xiao1; Yuan, Runzhu1,2; Zhou, Zhiqing1; Huang, Xin1; Zhang, Wei5; Su, Wenmei6; Lu, Yi1,4; Liang, Zhen2; Zhang, Jian1,4

2024

10.7150/ijbs.92046

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES   影响因子和分区

1449-2288

Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo. Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD.

lung adenocarcinoma chemoresistance CaSR BRCA1 cyclin B1 KIF11.

SCI

英语

第一 ; 通讯

NSFC["81972766","82173336","82073388","81972420"] ; Science and Technology Project of Shenzhen["JCYJ20190809161811237","JCYJ20210324104214040"] ; Natural Outstanding Youth Fund of Guangdong Province[2022B1515020090]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics

Biochemistry & Molecular Biology ; Biology

WOS:001272849100013

IVYSPRING INT PUBL

Web of Science

1.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Sch Med, Shenzhen 518055, Peoples R China
3.Univ Macau, Fac Hlth Sci, Taipa 999078, Macao, Peoples R China
4.Southern Univ Sci & Technol, Joint Lab Guangdong Hong Kong Univ Vasc Homeostasi, Sch Med, Shenzhen 518055, Guangdong, Peoples R China
5.Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Shenzhen 518055, Guangdong, Peoples R China
6.Guangdong Med Univ, Dept Pulm Oncol, Affiliated Hosp, Zhanjiang, Peoples R China

Wang, Fuhao,Fu, Xing,Chang, Ming,et al. The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2024,20(10).

Wang, Fuhao.,Fu, Xing.,Chang, Ming.,Wei, Tianzi.,Lin, Risheng.,...&Zhang, Jian.(2024).The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,20(10).

Wang, Fuhao,et al."The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 20.10(2024).