Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

作者全名：Shi, Yulu; Kang, Quan; Zhou, Hong; Yue, Xiaohan; Bi, Yang; Luo, Qing

作者地址：[Shi, Yulu; Zhou, Hong; Yue, Xiaohan; Bi, Yang; Luo, Qing] Childrens Hosp Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Stem Cell Biol & Therapy Lab, Minist Educ Key Lab Child Dev & Disorders,Chongqin, Chongqing 400014, Peoples R China; [Kang, Quan] Childrens Hosp Chongqing Med Univ, Dept Pediat Surg, Chongqing 400014, Peoples R China; [Luo, Qing] Childrens Hosp Chongqing Med Univ, Stem Cell Biol & Therapy Lab, Bldg 7,Room 905,136 Zhongshan Er Rd, Chongqing 400014, Peoples R China

通信作者：Luo, Q (通讯作者)，Childrens Hosp Chongqing Med Univ, Stem Cell Biol & Therapy Lab, Bldg 7,Room 905,136 Zhongshan Er Rd, Chongqing 400014, Peoples R China.

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001225704900001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：Cancer metabolism; Differentiation; LETM1; Osteosarcoma; Stemness

摘要：Osteosarcoma is a differentiation-deficient disease, and despite the unique advantages and great potential of differentiation therapy, there are only a few known differentiation inducers, and little research has been done on their targets. Cell differentiation is associated with an increase in mitochondrial content and activity. The metabolism of some tumor cells is characterized by impaired oxidative phosphorylation, as well as up-regulation of aerobic glycolysis and pentose phosphate pathways. Leucine-containing zipper and EF-hand transmembrane protein 1 (LETM1) is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression, as well as cancer cell stemness. We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function. Knockdown of LETM1 partially restored the mitochondrial structure and function, inhibited the pentose phosphate pathway, promoted oxidative phosphorylation, and led to osteogenic differentiation. It also inhibited spheroid cell formation, proliferation, migration, and invasion in an in vitro model. When LETM1 was knocked down in vivo, there was reduced tumor formation and lung metastasis. These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells, and knockdown of LETM1 partially restores the mitochondrial structure and function, inhibits the pentose

基金机构：National Nat-ural Science Foundation of China [81172545]; Chongqing Science and Technology Commission, China [cstc2020jcyj-msxmX0113]

基金资助正文：This work was supported by grants from the National Nat-ural Science Foundation of China (No. 81172545) and the Chongqing Science and Technology Commission, China (No. cstc2020jcyj-msxmX0113) .