Pancreatic cancer pkc

Fibroblast growth factor receptor (FGFR) signaling is a key modulator of cellular processes dysregulated in cancer. We recently found that the high expression of the mesenchymal FGFR2c variant in human pancreatic ductal adenocarcinoma (PDAC)-derived cells triggers the PKCε-mediated improvement of EMT and of MCL-1/SRC-dependent cell invasion. Since other membrane proteins can affect the receptor tyrosine kinase signaling, including transient receptor potential channels (TRPs), in this work, we investigated the role of TRPs in the FGFR2c/PKCε oncogenic axis...

Macropinocytosis has emerged as a nutrient-scavenging pathway that cancer cells exploit to survive the nutrient-deprived conditions of the tumor microenvironment. Cancer cells are especially reliant on glutamine for their survival, and in pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deficiency can enhance the stimulation of macropinocytosis, allowing the cells to escape metabolic stress through the production of extracellular-protein-derived amino acids. Here, we identify the atypical protein kinase C (aPKC) enzymes, PKCζ and PKCι as novel regulators of macropinocytosis...

An increasing number of studies have documented atypical protein kinase C isoform ι (PKCι) as an oncoprotein playing multifaceted roles in pancreatic carcinogenesis, including sustaining the transformed growth, prohibiting apoptosis, strengthening invasiveness, facilitating autophagy, as well as promoting the immunosuppressive tumor microenvironment of pancreatic tumors. In this study, we present novel evidence that PKCι overexpression increases STAT3 phosphorylation at the Y705 residue while decreasing STAT3 phosphorylation at the S727 residue in pancreatic cancer cells...

Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy...

Pancreatic ductal adenocarcinoma (PDAC) is the cancer with the poorest prognosis. One of the major properties reflecting its poor prognosis is high-grade heterogeneity, which leads to insensitivity to anticancer treatments. Cancer stem cells (CSCs) acquire phenotypic heterogeneity, generating abnormally differentiated cells by asymmetric cell division. However, the detailed mechanism leading to phenotypic heterogeneity is largely unknown. Here, we showed that PDAC patients with co-upregulation of PKCλ and ALDH1A3 had the poorest clinical outcome...

Introduction: The actin regulatory protein, cofilin plays a key signaling role in many cells for numerous cellular responses including in proliferation, development, motility, migration, secretion and growth. In the pancreas it is important in islet insulin secretion, growth of pancreatic cancer cells and in pancreatitis. However, there are no studies on its role or activation in pancreatic acinar cells. Methods: To address this question, we studied the ability of CCK to activate cofilin in pancreatic acinar cells, AR42J cells and CCK1 -R transfected Panc-1 cells, the signaling cascades involved and its effect on enzyme secretion and MAPK activation, a key mediator of pancreatic growth...

Being the fourth most fatal malignancy worldwide, pancreatic cancer is on track to become the second leading cause of cancer-related deaths in the United States by 2030. Gemcitabine is a first-line chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine Elaidate (Gem Elaidate) is a lipophilic derivative which allows hENT1-independent intracellular delivery of gemcitabine and better pharmacokinetics and entrapment in a nanocarrier. Cancer cells and neovasculature are negatively charged compared to healthy cells...

Aberrant DNA methylation is associated with oncogenesis of various human cancers, including pancreatic cancer (PC). PC is the seventh most common cancer, and obesity is a known high-risk factor. However, whether obesity influences DNA methylation in pancreatic exocrine cells and if this influences PC development remain unclear. Here, we performed an epigenome-wide analysis of isolated pancreatic exocrine cells obtained from mice with high-fat-diet-induced obesity (DIO). Using the Illumina Mouse Methylation BeadChip array (280K), we identified 316 differentially methylated regions (DMRs) that were enriched for cellular processes, such as DNA repair, transcription regulation, and cell proliferation, which confirmed obesity-related dysregulation of certain metabolic processes in the pancreatic cells in DIO mice...

Transient receptor potential (TRP) channels are one primary type of calcium (Ca2+ ) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive...

BACKGROUND: As the highest prevalent pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) ranks the 7th lethal malignancy worldwide. The late diagnosis, chemotherapeutic resistance, and high associated mortality make PDAC a dilemma facing the oncologists. Protein kinase C (PKC) enzymes have been shown to be important in different cancer progression. METHODS: To understand the pattern of PKC enzymes in PDAC, we examined all PKC family member genes expression in PDAC and matched normal tissues...

Pancreatic ductal adenocarcinoma (PDAC) is a treatment-resistant malignancy characterized by a high malignant phenotype including acquired EMT signature and deregulated autophagy. Since we have previously described that the aberrant expression of the mesenchymal FGFR2c and the triggering of the downstream PKCε signaling are involved in epidermal carcinogenesis, the aim of this work has been to assess the contribution of these oncogenic events also in the pancreatic context. Biochemical, molecular and immunofluorescence approaches showed that FGFR2c expression impacts on PDAC cell responsiveness to FGF2 in terms of intracellular signaling activation, upregulation of EMT-related transcription factors and modulation of epithelial and mesenchymal markers compatible with the pathological EMT...

The mechanism of pancreatic cancer (PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. This study was designed to investigate the role and mechanism of TRPM2 in pancreatic cancer. TRPM2 overexpressed and siRNA plasmid were created and transfected with pancreatic cancer cell line (BxPC-3) to construct the cell model. We employed CCK-8, Transwell, scratch wound, and nude mice tumor-bearing model to investigate the role of TRPM2 in pancreatic cancer...

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component...

Protein kinase signalling, which transduces external messages to mediate cellular growth and metabolism, is frequently deregulated in human disease, and specifically in cancer. As such, there are 77 kinase inhibitors currently approved for the treatment of human disease by the FDA. Due to their historical association as the receptors for the tumour-promoting phorbol esters, PKC isozymes were initially targeted as oncogenes in cancer. However, a meta-analysis of clinical trials with PKC inhibitors in combination with chemotherapy revealed that these treatments were not advantageous, and instead resulted in poorer outcomes and greater adverse effects...

Collagen triple helix repeat containing-1 (CTHRC1) has been identified as cancer-related protein. CTHRC1 expresses mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels and promotes cell migration and tissue repair in response to injury. CTHRC1 plays a pivotal role in some pathophysiological processes, including increasing bone mass, preventing myelination, and reversing collagen synthesis in many tumor cells. The ascended expression of CTHRC1 is related to tumorigenesis, proliferation, invasion, and metastasis in various human malignancies, including gastric cancer, pancreatic cancer, hepatocellular carcinoma, keloid, breast cancer, colorectal cancer, epithelial ovarian cancer, esophageal squamous cell carcinoma, cervical cancer, non-small-cell lung carcinoma, and melanoma...

OBJECTIVE: To study the impact of atypical protein kinase Cι (PKCι) isoform PKC on the pancreatic cancer cells towards the tumoricidal effect of cytokine-induced killer (CIK) cells and explore its mechanisms. METHODS: CIK cells were prepared by inducing mononuclear cells isolated from the peripheral blood of healthy people with interleukin-2 (IL-2), interferon (IFN) and CD3 mAb and subsequently co-cultured with pancreatic epithelial cell HPDE6-C7, pancreatic cancer cells MiaPaCa and PANC-1 with or without PKC inhibitor named sodium thiomalate (ATM)...

Protein kinase C (PKC)-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3 (Grx3; Glrx3)) is a ubiquitous protein that can interact with the embryonic ectoderm development (EED) protein via each of its two C-terminal PICOT/Grx homology domains. Since EED is a Polycomb-Group protein and a core component of the polycomb repressive complex 2 (PRC2), we tested the involvement of PICOT in the regulation of PRC2-mediated H3 lysine 27 trimethylation (H3K27me3), transcription and translation of selected PRC2 target genes...

BACKGROUND & AIMS: E-cadherin (Cdh1) is a key molecule for adherence required for maintenance of structural homeostasis. Loss of E-cadherin leads to poor prognosis and the development of resistance to chemotherapy in pancreatic cancer. Here, we evaluated the physiological and pathologic roles of E-cadherin in the pancreas. METHODS: We crossbred Ptf1a-Cre mice with Cdh1f /f mice to examine the physiological roles of E-cadherin in the pancreas. In addition, we crossbred these mice with LSL-KrasG12D/+ mice (PKC) to investigate the pathologic roles of E-cadherin...

The insulin-like growth factor 2 ( IGF2 ) mRNA binding protein IMP2 (IGF2BP2) is an oncogenic protein known to be overexpressed in different tumor types. Pancreatic cancer is a very lethal cancer that requires early diagnosis and new treatment options. The aim of our study was to investigate the role of IMP2 in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). IMP2 was significantly overexpressed in a human precursor (PanIN) lesions suggesting IMP2 as a marker for early stages of PDAC...

Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. β-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways...