Heng Lin

Taipei Medical University | TMU · Department of Physiology

Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilo...

Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilo...

The genetic and molecular basis underlying fear memory formation is a key theme in anxiety disorder research. Because activating transcription factor 3 (ATF3) is induced under stress conditions and is highly expressed in the hippocampus, we hypothesise that ATF3 plays a role in fear memory formation. We used fear conditioning and various other para...

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate...

High insulin/IGF is a biologic link between diabetes and cancers, but the underlying molecular mechanism remains unclear. Here we report a previously unrecognized tumour-promoting mechanism for stress protein TRB3, which mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin/IGF to malignant pro...

B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor, involves in the development and progression of breast cancers with uncertain mechanism. The purpose of this study is to investigate the potential effect and mechanism of BCL6 in the regulation of epithelial-mesenchymal transition (EMT), a critical cellular process for controlling the develo...

Cell-penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. In this study, enhanced expression of toll like receptor 2 (TLR2) was observed in acute myeloid leukemia (AML) cells. Screening of a phage display peptide library using Bio-panning and Rapid Analysis...

Hepatocellular carcinoma (HCC) remains one of the most deadly solid tumor malignancies worldwide. We recently find that the loss of toll-like receptor 2 (TLR2) activities promotes the diethylnitrosamine (DEN) induced hepatocellular carcinogenesis and tumor progression, which associates with an abundant accumulation of reactive oxygen species (ROS)...

Hepatocellular carcinoma (HCC) is a complication at the endstage of chronic inflammatory liver diseases with dismal prognosis. Targeting of Toll-like receptor (TLR) 2 attenuates tu-mor metastases; we hypothesized that blocking TLR2 might also play a crucial role in reducing hepatocarcinogenesis. Surprisingly, we found that the genetic deletion of T...

Unlabelled: Hepatocellular carcinoma (HCC) is a devastating consequence of chronic inflammatory liver diseases. The goal of this study was to investigate whether Toll-like receptor 4 (TLR4) activity contributes to HCC initiation and progression in mice. A mouse model of diethylnitrosamine (DEN)-induced HCC was generated with wild-type and TLR4 mut...

To prepare large naive phage antibody library, the host bacteria with high transformation efficiency is used in the Cre-LoxP recombination system. The variable regions of immunoglobulin light and heavy genes were amplified from lymphocytes collected from adult peripheral blood and newborn cord blood. The genes were spliced to form the single-chain...

Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. The initiation and progression of HCC is closely associated with chronic liver inflammation. Recent research indicates that nonhomologous end joining (NHEJ), one of the DNA repair mechanisms, autophagy and senescence are all involved in the pathog...

With the development of therapeutic antibodies over the past decade, they have become the treatment options for immunity and inflammation diseases. Major limitations of mouse antibodies as therapeutic agents - immunogenicity, lack of effectors' functions and short serum half-life -- were subsequently identified and largely overcome by the advent of...

Hepatocellular carcinoma (HCC), the most common primary malignant liver tumor, is the third leading cause of cancer deaths. The pathogenesis of HCC is closely associated with chronic liver inflammation fired by a variety of stimulates such as virus infection and metabolic stress. Recent work indicates that autophagy, a homeostatic self-degradation...

Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversel...

Recombinant single-chain variable fragment (scFv) antibodies have wide applications in the areas of biotechnology and medicine. However, there is currently no universal expression-purification system for generating different soluble scFvs. In this study, A15 and E34, two genes coding scFvs against human IL-17A, were fused with N-terminal signal pep...

Tribbles homolog 3 (TRB3, also known as TRIB3, NIPK and SKIP3), a human homolog of Drosophila Tribbles, has been found to interact with a variety of signaling molecules to regulate diverse cellular functions. Here, we report that TRB3 is a novel SMAD3-interacting protein. Expression of exogenous TRB3 enhanced the transcriptional activity of SMAD3,...

Glycogen synthase kinase-3beta (GSK3beta) is a major negative modulator of cardiac hypertrophy. Here we report that GSK3beta physically and functionally interacts with Smad3. The interaction between GSK3beta and Smad3 may participate in the negative regulation of transforming growth factor beta1 (TGF-beta1) and Angiotensin II-induced transcription...

Transforming growth factor-beta1 (TGF-beta1) regulates a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Here we report that death effector domain-containing DNA-binding protein (DEDD) physically interacts with Smad3. The inhibition of Smad3 by DEDD resulted in a reduction in TGF-beta1/Smad3-medi...

Supplemental material and methods (0.06 MB DOC)

Pam3Cys enhanced the release of cytokines, chemokines and the expression of chemokine receptors by B16 melanomas in vitro. B16 cells were pretreated with TLR2- or TLR4- shRNA for 16 hs before the addition of ultra-purified Pam3Cys (1 µg/mL). After incubation for 24 h, the expressions of IL-6 (A), IL-10 (B), IL-13 (C), TGF-Î21 (D) and MCP-1 (E) wer...

Activation of Stat3 mediated Pam3Cys stimulation of gene expression involved in tumor progression and metastasis. B16 cells were pretreated with a Stat3I (10 µg/mL) for one hour before the addition of Pam3Cys (1 µg/mL). Otherwise, B16 cells with or without Stat3C (S3C) vector were treated with TLR2 shRNA for 16 h after transfection. After incubat...

TLR2 mediated the HSP60 induced expressions of suppressive cytokines, chemokines and chemokine receptors. B16 cells were pretreated with a TLR2 shRNA 16 hs before the addition of HSP60 (20 ng/mL). After incubation for 24 h, the levels of IL-6 (A), IL-10 (B), IL-13 (C), TGF-β1 (D) and MCP-1 (E) were determined with intracellular flow cytometry. The...

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TLR2 expressed on tumor cells. (A-B) The expression of TLR2 and TLR4 on B16 cells was detected by immunofluorescence microscopy (A) or by immunoblot (B). (C) The expression profile of TLR1-9 mRNAs in B16 cells was detected by RT-PCR. (D) Knockdown of TLR2 did not change the growth of B16 cells (E) TLR2 expressed on several human tumor cell lines, i...

HSP60 released by B16 cells maintained the constitutive activity of Stat3 through activation of TLR2. (A) High metastatic B16-F10 cells produced much more HSP60 than low metastatic B16-F1 cells. The B16-F10 cells and B16-F1 cells were cultured in a medium containing different concentrations of serum. After incubation for 24 h, the supernatants were...

Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis. In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells. Multiple subtypes of TLRs were express...