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SEMG1/2 augment energy metabolism of tumor cells.
- Source :
-
Cell death & disease [Cell Death Dis] 2020 Dec 11; Vol. 11 (12), pp. 1047. Date of Electronic Publication: 2020 Dec 11. - Publication Year :
- 2020
-
Abstract
- SEMG1 and SEMG2 genes belong to the family of cancer-testis antigens (CTAs), whose expression normally is restricted to male germ cells but is often restored in various malignancies. High levels of SEMG1 and SEMG2 expression are detected in prostate, renal, and lung cancer as well as hemoblastosis. However, the functional importance of both SEMGs proteins in human neoplasms is still largely unknown. In this study, by using a combination of the bioinformatics and various cellular and molecular assays, we have demonstrated that SEMG1 and SEMG2 are frequently expressed in lung cancer clinical samples and cancer cell lines of different origins and are negatively associated with the survival rate of cancer patients. Using the pull-down assay followed by LC-MS/MS mass-spectrometry, we have identified 119 proteins associated with SEMG1 and SEMG2. Among the SEMGs interacting proteins we noticed two critical glycolytic enzymes-pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Importantly, we showed that SEMGs increased the protein level and activity of both PKM2 and LDHA. Further, both SEMGs increased the membrane mitochondrial potential (MMP), glycolysis, respiration, and ROS production in several cancer cell lines. Taken together, these data provide first evidence that SEMGs can up-regulate the energy metabolism of cancer cells, exemplifying their oncogenic features.
- Subjects :
- Carrier Proteins metabolism
Cell Line, Tumor
Cell Respiration
Gene Expression Regulation, Neoplastic
Glycolysis
HEK293 Cells
Humans
Lactate Dehydrogenase 5 metabolism
Lung Neoplasms genetics
Lung Neoplasms metabolism
Membrane Potential, Mitochondrial
Membrane Proteins metabolism
Models, Biological
Neoplasms genetics
Protein Binding
RNA, Messenger genetics
RNA, Messenger metabolism
Reactive Oxygen Species metabolism
Seminal Vesicle Secretory Proteins genetics
Survival Analysis
Thyroid Hormones metabolism
Treatment Outcome
Up-Regulation genetics
Thyroid Hormone-Binding Proteins
Energy Metabolism genetics
Neoplasms metabolism
Seminal Vesicle Secretory Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 11
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 33311447
- Full Text :
- https://doi.org/10.1038/s41419-020-03251-w