Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.
Journal of Hepatology 65(2):325 (2016)
Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability ...
Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer.
Cell Reports 15(7):1493 (2016)
3q26.2 amplification in high-grade serous ovarian cancer leads to increased expression of mature microRNA miR551b-3p, which is associated with poor clinical outcome. Importantly, miR551b-3p contributes to resistance to apoptosis and increased survival and proliferation of cancer cells in vitro a...
Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.
Journal of Clinical Investigation 126(5):1834 (2016)
Targeting multiple components of the MAPK pathway can prolong the survival of patients with BRAFV600E melanoma. This approach is not curative, as some BRAF-mutated melanoma cells are intrinsically resistant to MAPK inhibitors (MAPKi). At the systemic level, our knowledge of how signaling pathway...
HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors.
Cancer Research 76(9):2720 (2016)
The stress-inducible chaperone protein HSP70 (HSPA1) is implicated in melanoma development, and HSP70 inhibitors exert tumor-specific cytotoxic activity in cancer. In this study, we documented that a significant proportion of melanoma tumors express high levels of HSP70, particularly at advanced...
Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies.
Clinical Cancer Research 22(7):1592 (2016)
To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models.
We established 12 PDXs from BRAF inhibitor-progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and reverse-...
Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma.
Cell Reports 14(10):2476 (2016)
On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression), we classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes. Site of origin within the nephron...
MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Antiestrogen Resistance in ER-Positive High-Grade Serous Ovarian Cancer.
Clinical Cancer Research 22(4):935 (2016)
Although 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in ovarian cancer, we investigated if estrogen regulates MAPK and if MEK inhibition (MEKi) reverses antiestrogen resistance.
Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid Endometrial Cancer.
Clinical Cancer Research 22(2):513 (2016)
Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recur...
Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
New England Journal of Medicine 374(2):135 (2016)
Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is kno...
Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway.
Scientific reports 6:27391 (2016)
Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A e...
YAP/TAZ regulates the insulin signaling via IRS1/2 in endometrial cancer.
American journal of cancer research 6(5):996 (2016)
Insulin resistance (IR) is an important mechanism of pathogenesis of endometrial cancer (EC) and explains the pathogenic mechanism of high risk factors including Obesity BMI (body mass index), Type 2 Diabetes Mellitus, PCOS and so on. Relieving IR or inhibiting the function of insulin could be o...
Glucose starvation induces mutation and lineage-dependent adaptive responses in a large collection of cancer cell lines.
International Journal of Oncology 48(1):67 (2016)
Tolerance of glucose deprivation is an important factor for cancer proliferation, survival, migration and progression. To systematically understand adaptive responses under glucose starvation in cancers, we analyzed reverse phase protein array (RPPA) data of 115 protein antibodies across a panel...
Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.
American journal of cancer research 6(1):27 (2016)
Yes-associated protein (YAP), the central mediator of Hippo pathway, not only regulates a diversity of cellular processes during development but also plays a pivotal role in tumorigenesis. YAP is overexpressed in many types of human cancers with its expression level being associated with patient...
Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers.
Cancer Cell 28(4):529 (2015)
The discovery of long non-coding RNA (lncRNA) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of lncRNA alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atl...
The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers.
Cancer Cell 28(4):515 (2015)
Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from...
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
New England Journal of Medicine 372(26):2481 (2015)
Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to g...
Development of a robust classifier for quality control of reverse-phase protein arrays.
High-throughput reverse-phase protein array (RPPA) technology allows for the parallel measurement of protein expression levels in approximately 1000 samples. However, the many steps required in the complex protocol (sample lysate preparation, slide printing, hybridization, washing and amplified ...
[Construction of novel thioredoxin fusion protein expression system and the production of recombinant Lf-CATH2].
Chinese Journal of Biotechnology/Shengwu Gongch... 31(3):403 (2015)
The objective of this study was to construct an improved thioredoxin fusion protein expression system, and express the cathelicidin-derived peptide, Lf-CATH2. The improved fusion vector Lf-CATH2-pET32α(-TS) was successfully constructed by firstly deleting the thrombin site and S tag from the pET...
Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.
Genome Research 25(2):257 (2015)
We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-targ...
α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration.
Cancer Research 75(1):203 (2015)
Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic p...