CDK1 dependent phosphorylation of hTERT contributes to cancer progression.

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses reveal that phosphorylation of hTERT at threonine 249 occurs more frequently in aggressive cancers.

Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors.

Purpose: The purpose is to examine whether patient-derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients.

Experimental Design: To characterize patient-derived models for functional studies, proteomic comparisons with originating sarcomas representative of three intrinsic subtypes by MS are performed.

Results: Human protein profiling is found to be retained with high fidelity in patient-derived models.

HDAC2 Regulates Site-Specific Acetylation of MDM2 and Its Ubiquitination Signaling in Tumor Suppression.

Histone deacetylases (HDACs) are promising targets for cancer therapy, although their individual actions remain incompletely understood. Here, we identify a role for HDAC2 in the regulation of MDM2 acetylation at previously uncharacterized lysines. Upon inactivation of HDAC2, this acetylation creates a structural signal in the lysine-rich domain of MDM2 to prevent the recognition and degradation of its downstream substrate, MCL-1 ubiquitin ligase E3 (MULE).

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1.

Dedifferentiated chondrosarcoma is an aggressive mesenchymal tumor of the bone, and novel therapies are needed to improve its clinical outcomes. Patient-derived cell lines are essential tools for elucidating disease mechanisms associated with poor prognosis and for developing therapies. However, few lines and xenografts have been previously reported in dedifferentiated chondrosarcoma.

Establishment and characterization of a novel cell line, NCC-MFS1-C1, derived from a patient with myxofibrosarcoma.

Myxofibrosarcoma (MFS) is an aggressive sarcoma that requires novel therapeutic approaches to improve its clinical outcome. Cell lines are a valuable tool for pre-clinical research; however, there is a lack of patient-derived cell lines of MFS available from public cell banks. This study aimed to develop a patient-derived cell line of MFS.

Pazopanib-induced changes in protein expression signatures of extracellular vesicles in synovial sarcoma.

Secreted proteins enclosed in extracellular vesicles can act as intercellular messengers. The objective of this study was to elucidate the role of proteins secreted from synovial sarcoma cells in the regulatory network underlying pazopanib response. We performed a comprehensive analysis of expression of proteins secreted from four synovial sarcoma cell lines (SYO-1, HS-SYII, 1273/99, and YaFuSS) using mass spectroscopy.

Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1.

Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor β (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research.

Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line.

Osteosarcoma is an aggressive mesenchymal malignancy of the bone. Patient-derived models are essential tools for elucidating the molecular mechanisms associated with poor prognosis and the development of novel anticancer drugs. This study described the establishment of a patient-derived cancer model of osteosarcoma.

Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone.

Primary leiomyosarcoma (LMS) of bone is a rare and aggressive mesenchymal malignancy that differentiates toward smooth muscle. Complete resection is the only curable treatment, and novel therapeutic approaches for primary LMS of bone have long been desired. Patient-derived xenografts (PDXs) and cell lines are invaluable tools for preclinical studies.

Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1.

Synovial sarcoma is an aggressive mesenchymal tumor, characterized by the presence of unique transfusion gene, SS18-SSX. Cell lines enable researchers to investigate the molecular backgrounds of disease and the significance of SS18-SSX in relevant cellular contexts. We report the establishment and proteomic characterization of a novel synovial sarcoma cell line.

Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line.

Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line.

Establishment and proteomic characterization of a novel cell line, NCC-UPS2-C1, derived from a patient with undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy requiring novel therapeutic approaches to improve clinical outcome. Patient-derived cancer cell lines are an essential tool for investigating molecular mechanisms underlying cancer initiation and development; however, there is a lack of patient-derived cell lines of UPS available for research. The objective of this study was to develop a patient-derived cell model of UPS.

Proteomic approach toward determining the molecular background of pazopanib resistance in synovial sarcoma.

Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS.

Establishment and proteomic characterization of patient-derived clear cell sarcoma xenografts and cell lines.

Clear cell sarcoma (CCS) is an aggressive mesenchymal malignancy characterized by the unique chimeric EWS-ATF1 fusion gene. Patient-derived cancer models are essential tools for the understanding of tumorigenesis and the development of anti-cancer drugs; however, only a limited number of CCS cell lines exist. The objective of this study was to establish patient-derived CCS models.

Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma.

The development of drug resistance in tumor cells leads to relapse and distant metastasis. Secreted microRNAs (miRNAs) enclosed in extracellular vesicles (EVs) can act as intercellular messengers. The objective of our study was to elucidate the role of secreted miRNAs to better understand the regulatory network underlying pazopanib-resistance in synovial sarcoma cells.

Establishment and proteomic characterization of NCC-LMS1-C1, a novel cell line of primary leiomyosarcoma of the bone.

Background: Leiomyosarcoma (LMS) is one of most aggressive mesenchymal malignancies that differentiate towards smooth muscle. The clinical outcome of LMS patients is poor; as such, there is an urgent need for novel therapeutic approaches. Experimental models such as patient-derived cell lines are invaluable tools for pre-clinical studies.

Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines.

CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression. CDS exhibits an aggressive course and poor clinical outcome, thus novel therapeutic approaches are needed for CDS treatment. Although patient-derived cancer models are an essential modality to develop novel therapies, none currently exist for CDS.

Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction.

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis of the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function in spermatogenesis has been recently elucidated.

Solution structure of human Pex5.Pex14.PTS1 protein complexes obtained by small angle X-ray scattering.

The Pex5p receptor recognizes newly synthesized peroxisomal matrix proteins which have a C-terminal peroxisomal targeting signal to the peroxisome. After docking to protein complexes on the membrane, these proteins are translocated across the membrane. The docking mechanism remains unclear, as no structural data on the multicomponent docking complex are available.

The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97.

PEX1 is a type II AAA-ATPase that is indispensable for biogenesis and maintenance of the peroxisome, an organelle responsible for the primary metabolism of lipids, such as beta-oxidation and lipid biosynthesis. Recently, we demonstrated a striking structural similarity between its N-terminal domain and those of other membrane-related AAA-ATPases, such as valosine-containing protein (p97). The N-terminal domain of valosine-containing protein serves as an interface to its adaptor proteins p47 and Ufd1, whereas the physiologic interaction partner of the N-terminal domain of PEX1 remains unknown.

Crystallographic characterization of the N-terminal domain of PEX1.

Peroxisomal enzymes are responsible for several primary metabolism pathways, including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are hexameric AAA-type ATPases and both are necessary for the import of more than 50 peroxisomal resident proteins from the cytosol into peroxisomes. In this study, PEX1 N-terminal domain crystals have been prepared.

Structure of the N-terminal domain of PEX1 AAA-ATPase. Characterization of a putative adaptor-binding domain.

Peroxisomes are responsible for several pathways in primary metabolism, including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are hexameric AAA-type ATPases, both of which are indispensable in targeting over 50 peroxisomal resident proteins from the cytosol to the peroxisomes. Although the tandem AAA-ATPase domains in the central region of PEX1 and PEX6 are highly similar, the N-terminal sequences are unique.