Ching-Wen Chang

Graduate Institute of Metabolism and Obesity Sciences (GIMOS)

During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expres...

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease worldwide but only a subset of NAFLD individuals may progress to nonalcoholic steatohepatitis (NASH). While NASH is an important etiology of hepatocellular carcinoma (HCC), the underlying mechanisms responsible for conversion of NAFLD to NASH, and th...

Background and aims: Purines are building blocks for cellular genome and excessive purine nucleotides are seen in tumors. However, how purine metabolism is dysregulated in tumor and impacting tumorigenesis remains elusive. Approach and results: Transcriptomic and metabolomic analysis of purine biosynthesis and purine degradation pathways were pe...

Introduction Purines are building blocks for genomics and the abundance of purine nucleotides is controlled by purine synthesis and purine degradation. Imbalance of purine nucleotide pool in tumors has been shown, but how synthesis and degradation of purine integrates in tumors has not been well characterized. Hepatocellular carcinoma (HCC) is the...

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease worldwide and may progress to nonalcoholic steatohepatitis (NASH). Although emerging evidence suggests that NASH would be an important driver of hepatocellular carcinoma (HCC), molecularly what drives the transition of NAFLD to NASH and then HCC has not been clearly d...

Mitochondria are major organelles responsible for cellular energy and metabolism, and their dysfunction is tightly linked to cancer. The mitochondrial ribosome (mitoribosome) is a protein complex consisting of 82 mitoribosomal proteins (MRPs) encoded by nuclear genes and is essential for mitochondrial protein synthesis. However, how their roles in...

Background & Aims Hepatocellular carcinoma (HCC) is characterized by intratumoral accumulation of regulatory T-cells (Tregs), which suppresses antitumor immunity. This study was designed to investigate how microRNAs regulate immunosuppression in HCC. Methods FVB/NJ mice were hydrodynamically injected with AKT/Ras or c-Myc and Sleeping Beauty trans...

Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a significant risk factor to drive hepatocellular carcinoma (HCC). However, a preclinical model of progressive NAFLD/NASH is largely lacking. Here, we report that mice with hepatocyte specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HC...

Background & aims: Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Here, we aimed to determine what drives tumor cell evolution by performing single-cell transcriptomic analysis. Methods: We analyzed 46 hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinom...

T-cell exhaustion denotes a hypofunctional state of T lymphocytes commonly found in cancer, but how tumor cells drive T-cell exhaustion remains elusive. Here, we find T-cell exhaustion linked to overall survival in 675 hepatocellular carcinoma (HCC) patients with diverse ethnicities and etiologies. Integrative omics analyses uncover oncogenic repro...

Tid1, a mitochondrial co-chaperone protein, acts as a tumor suppressor in various cancer types. However, the role of Tid1 in hepatocellular carcinoma (HCC) remains unclear. First, we found that a low endogenous Tid1 protein level was observed in poorly differentiated HCC cell lines. Further, upregulation/downregulation of Tid1 abrogated/promoted th...

Tumor evolution is a key feature intrinsic to tumor biology and contributes to intratumor heterogeneity, escape of immune surveillance, treatment failure, and patients’ prognosis. The evolutionary process of tumor is driven by selecting favorable phenotypes in terms of their fitness and survival in a tumor ecosystem. While genomic alterations provi...

Tumor evolution is a key feature of tumorigenesis and plays a pivotal role in driving intratumor heterogeneity, treatment failure and patients' prognosis. Here we performed single-cell transcriptome profiling of 46 primary liver cancers from 37 patients enrolled for interventional studies. We surveyed the landscape of ~57,000 malignant and non-mali...

Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA)or acetyl-CoA by Pyruvate D...

Summary for impacts of LDHA/PDH in controlling tumorigenesis

Primary liver cancer (PLC) is heterogeneous and it is an aggressive malignancy with a poor prognostic outcome. Current evidence suggests that PLC tumorigenesis is driven by rare subpopulations of cancer stem cells (CSCs), which contribute to tumor initiation, progression, and therapy resistance through particular molecular mechanisms. Energy metabo...

Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor. Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy. However, the molecular details of Tid1-mediated anti-metastasis remain elusive. Methods: We used affinity chromatography and systemic mass spec...

Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROSLow cells) display enhanced features of CICs. However,...

Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME)...

Background: Cancer-initiating cells (CICs) contribute to tumor initiation, progression and therapy resistance through critical physiology mechanisms. Redox homeostasis plays an important role in the regulation of cancer stemness. We recently have reported that cancer cells containing differential level of ROS display distinct physiological properti...

Head and neck cancer (HNC) is one of the most common forms of cancer in Taiwan. In addition, head and neck cancer cells (HNCs) are highly tumorigenic and resistant to conventional therapy. Therefore, development of new therapeutic regimens that are adjuvant to conventional treatments would benefit future head and neck cancer therapy. In this study,...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Cancer initiating cells (CICs), also termed as Cancer stem cells (CSCs), represent a rare subpopulation of cells, which are responsible for tumor growth. CICs such as head and neck cancer initiating cells (HN-CICs), are often resistant to either radio- or chemotherap...

Head and neck squamous cell carcinoma (HNSCC) is a lethal cancer. Emerging evidence supports cancer-initiating cells (CICs) are responsible for tumor growth, chemoresistance, etc. However, the physiological mechanisms by which to maintain the characteristics of CICs in HNSCC (HN-CICs) remain elusive. For hematopoietic stem cells, low intracellular...

Supplementary Table 1. Effect of YMGKI-1 Treatment on Cancer Cell Lines Supplementary Figure S1. YMGKI-1 affected the cell viability of SAS-HN-CICs (1 × 107 cells/well of 6-well plate) but not parental SAS (5 × 105 cells/well of 6-well plate). A, Cells were treated with 0, 10, 25, 35 and 50 μg/ml of YMGKI-1 for 24 hr, afterward, stained with propid...

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer. Previously, we identify head and neck cancer initiating cells (HN-CICs), which are highly tumorigenic and resistant to conventional therapy. Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. In this stu...

Background: Cancer stem cells (CSCs), also termed as Cancer initiating cells (CICs), represent a rare subpopulation of cells, which are responsible for tumor growth. CICs such as oral cancer -cancer initiating cells (OC-CICs), are often resistant to either radio- or chemotherapy. Therefore, development of drug candidates that specifically target OC...

Background: Cancer initiating cells (CICs) represent a rare subpopulation of cancer cells, which are responsible for tumor growth. Cancer initiating cells such as oral cancer-cancer initiating cells (OC-CICs), are often resistant to either radiotherapy or chemotherapy. Therefore, screening and development for drug candidates that target OC-CICs spe...