2. Academic Validation
  3. LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10

LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10

  • Cancer Gene Ther. 2023 Oct 27. doi: 10.1038/s41417-023-00680-5.
Dongdong Tong # 1,  Jun Zhou # 2,  Jing Zhou 1,  Xiaofei Wang 3,  Beibei Gao 1,  Xiaoyi Rui 1,  Liying Liu 3,  QiaoYi Chen 4,  Chen Huang 5 6 7
Affiliations

Affiliations

  • 1 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 710061, Xi'an, Shaanxi, China.
  • 2 Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China.
  • 3 Biomedical Experimental Center of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China.
  • 4 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 710061, Xi'an, Shaanxi, China. qychen203@xjtu.edu.cn.
  • 5 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 710061, Xi'an, Shaanxi, China. hchen@xjtu.edu.cn.
  • 6 Biomedical Experimental Center of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China. hchen@xjtu.edu.cn.
  • 7 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, 710061, Xi'an, China. hchen@xjtu.edu.cn.
  • # Contributed equally.
PMID: 37891404 DOI: 10.1038/s41417-023-00680-5
Abstract

Highly proliferative and metastatic tumors are constantly exposed to both intrinsic and extrinsic factors that induce adaptation to stressful conditions. Chronic adaptation to endoplasmic reticulum (ER) ER stress is common to many different types of cancers, and poses a major challenge for acquired drug resistance. Here we report that LAMC2, an extracellular matrix protein upregulated in many types of cancers, is localized in the ER of lung, breast, and liver Cancer cells. Under tunicamycin-induced ER stress, protein level of LAMC2 is upregulated. Transfection of Cancer cells with LAMC2 resulted in the attenuation of ER stress phenotype, accompanied by elevation in mitochondrial membrane potential as well as reduction in Reactive Oxygen Species (ROS) levels and Apoptosis. In addition, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region. Moreover, overexpression of LAMC2 counteracts the effects of ER stress and promotes tumor growth in vivo. Taken together, our results revealed that in complex with MYH9 and MYH10, LAMC2 is essential for promoting ER-mitochondria interaction to alleviate ER stress and allow Cancer cells to adapt and proliferate under stressful conditions. This study provides new insights and highlights the promising potential of LAMC2 as a therapeutic target for Cancer treatment.

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