Among the genes that were found to be abundantly overexpressed in highly metastatic rat cell lines compared to poorly metastatic cell lines, we identified a completely novel complementary DNA (cDNA) without any homologous or related genes in the database in 1994. The full-length cDNA of this rat gene was cloned, sequenced, and named metastasis-associated gene 1 (mta1), and eventually, its human cDNA counterpart, MTA1, was also cloned and sequenced by our group. MTA1 has now been identified as one of the members of a gene family (MTA gene family) and the products of the MTA genes, the MTA proteins, are transcriptional co-regulators that function in histone deacetylation and nucleosome remodeling and have been found in nuclear histone remodeling complexes. Furthermore, MTA1 along with its protein product MTA1 has been repeatedly and independently reported to be overexpressed in a vast range of human cancers and cancer cell lines compared to non-cancerous tissues and cell lines. The expression levels of MTA1 correlate well with the malignant properties of human cancers, strongly suggesting that MTA1 and possibly other MTA proteins (and their genes) could be a new class of molecular targets for cancer diagnosis and therapy.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s10555-014-9516-2 | DOI Listing |
Sci Adv
January 2025
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.
View Article and Find Full Text PDFSci Adv
January 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
NF2-related schwannomatosis, previously known as neurofibromatosis type 2, is a genetic disorder characterized by nerve tumors due to gene mutations. Mice with deletion develop schwannomas slowly with low penetrance, hence inconvenient for preclinical studies. Here, we show that NF2, by recruiting E3 ubiquitin ligases β-TrCP1/2, promotes WWC1-3 ubiquitination and degradation.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multiomic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in and mutants, where lysosomes accumulate cholesterol.
View Article and Find Full Text PDFShock
February 2025
Department of Respiratory and Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Background: Ubiquitination and deubiquitination are involved in the progression of human diseases, including acute pneumonia. In this study, we aimed to explore the functions of ubiquitin-specific peptidase 9X-linked (USP9X) in lipopolysaccharide (LPS)-treated WI-38 cells. Methods: WI-38 cells were treated with LPS to induce the cellular damage and inflammation.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!