Learn About the Causes of Pancreatic Cancer and How It Can Be Treated. Read More About Pancreatic Cancer, Including Early Detection & Treatment Options Pancreatic cancer is in the top 10 list of most common types of cancer in men and women. It is also in the top 5 list of leading causes of cancer-related deaths. In other words Plectin is a regulator of prostate cancer growth and metastasis Plectin is a regulator of prostate cancer growth and metastasis Oncogene. 2020 Nov 20. doi: 10.1038/s41388-020-01557-9. Online ahead of print In pancreatic ductal adenocarcinoma, plectin is essential for exosome production and promotes cancer growth 44. In this study, we demonstrate that high levels of plectin are observed across prostate cancer xenografts tissues, as well as in human localized and metastatic prostate cancer Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma J Proteomics. 2012 Mar 16;75(6):1803-15. doi: 10.1016/j.jprot.2011.12.018. Epub 2011 Dec 30. Authors Koji Katada 1.
Pancreatic carcinoma cell lines expressing plectin-1 were cultured with the targeted or control probes and then were imaged using confocal laser scanning microscopy and magnetic resonance imaging (MRI). Accumulations of the nanoparticles in pancreatic tumor xenografted mice were determined by MRI and fluorescence imaging This cancer specific phenotype allowed us to image pancreatic cancer successfully using plectin targeted peptide (PTP) conjugated to nanoparticles or displayed on capsid protein of adeno-associated virus (AAV) particles
Here, we demonstrate that high levels of plectin are associated with localized and metastatic human prostate cancer when compared to benign prostate tissues. Knock-down of plectin inhibits prostate.. BACKGROUND: Biomarker-targeted molecular imaging holds promise for early detection of pancreatic cancer. The aim of this study was to design and evaluate a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer imaging
. RON protein was IP in the presence and absence of MSP and coprecipitated proteins underwent Mud-PIT analysis Plectin knock-down inhibits prostate cancer cell growth in vitro and in vivo. To determine the role of plectin in tumorigenesis, we generated stable plectin knock-down DU145 and C4-2 cell lines. pancreatic cancer biomarker, Plectin-1, that distin-guishes PDAC from benign inflammatory diseases such aschronicpancreatitis.Plectin-1isidentifiedin100%of tested PDAC tumors and 60% of preinvasive PanIN III lesions, and is retained in metastatic deposits, charac-teristics needed for an ideal imaging biomarker. In viv Plectin-1 targeted dual-functional nanoparticle has great potential in pancreatic cancer detection. Molecular-based radiographic tests hold the promise to help precisely identifying pancreatic malignant lesions and their precursors at early stages
To treat metastatic breast cancer, the study authors suggested, it may be possible to target the RNA splice site that generates the invasion-promoting variant of plectin with small bits of. Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background & Aims: We recently demonstrated that the aberrant extracellular localization of the cytoskeletal linker protein plectin is a robust biomarker for the progression of pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. Exosomes are nanometer-sized particles containing cytoplasm. When the peptoids were used to pulldown their targets, one was revealed to be plectin, showing that there are both genotypic and phenotypic correlations between the protein and lung cancer stem cells. Furthermore, high plectin expression in patients was linked to poor survival rates, say the researchers, linking the protein even further Plectin-1 targeted dual-functional nanoparticle has great potential in pancreatic cancer detection. Molecular-based radiographic tests hold the promise to help precisely identifying pancreatic malignant lesions and their precursors at early stages. Previous studies showed that plectin-1 highly expressed in pancreatic ductal adenocarcinoma but.
ZielBio's lead candidate ZB131 is a proprietary humanized monoclonal antibody against cancer specific plectin (CSP), a target that is highly expressed on the plasma membrane of multiple types of cancer cells, including several with high unmet need. ZielBio plans to launch its first clinical trial of ZB131 in late 2021 Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma. Author links open overlay panel Koji Katada a Takeshi Tomonaga b c Mamoru Satoh c Kazuyuki Matsushita c Yurie Tonoike a Yoshio Kodera d Toyoyuki Hanazawa a Fumio Nomura c Yoshitaka Okamoto a This is the first demonstration of a viral vector with pancreatic cancer cell specificity. The Plectin-1 Targeted Peptide (PTP) modified AAV2 capsid was shown to localize to tumor xenografts in mice indicating that the natural tropism of the AAV2 capsid for hepatocytes was dramatically altered .Many of them have plectin - a protein normally found in cells' interior cytoskeletons- on their surface. We don't know how plectin gets on the surface of cancer cells, but we do know. Plectin is a regulator of prostate cancer growth and metastasis. Coronavirus: Find the latest articles and preprints Sign in or create an account. https://orcid.org. Europe PMC Search examples: breast cancer Smith J. Recent history Saved searches.
. Scientific Reports , 2019; 9 (1) DOI: 10.1038/s41598-019-51004-3 Cite. Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer Soo J. Shina,b, Jeffrey A. Smitha,b, Günther A. Rezniczekc,d, Sheng Pane, Ru Chene, Teresa A. Brentnalle, Gerhard Wichec, and Kimberly A. Kellya,b,1 aDepartment of Biomedical Engineering, University of Virginia School of Engineering and Applied Sciences, Charlottesville, VA 22908. In a new study published online in Science on May 14, researchers led by Hani Goodarzi, PhD, an assistant professor in the Department of Biochemistry and Biophysics and a member of the UCSF Helen Diller Family Comprehensive Cancer Center, determined that a specific variant of a protein called plectin is overproduced as a result of abnormal alternative splicing in many cases of metastatic.
Or cancer of any other origin, especially after you have done 3 rounds of chemo or 7 rounds of chemo & radiation! Odds are it's over! Close the shades, update your will, finalize your funeral arrangements, and kiss your family and friends goodbye. Well, I knew all of that! Having seen it 1st hand as I watched my mother die from metastasized. Results and discussion Examination of the expression levels of plectin-1 in pancreatic cells and tumor tissues. Plectin-1 has been proposed as a biomarker for pancreatic cancer [, , ].Specific expression of plectin-1 on pancreatic tumor cells is also the premise for designing plectin-1 targeting nanoparticles
Because plectin assists in shaping cells, it is pivotal to the spread of cancer, helping cancer stem cells wend their way through the body. Scientists are desperately trying to find ways to handle these stubborn cancer stem cells to wipe out tumours We have found a new biomarker, the protein plectin, on cancer stem cells. We believe plectin may be a more common biomarker that could lead to broadly applicable drug development, reports Gomika. Previous research found that plectin deficiencies reduced the mobility and invasiveness of pancreatic, urinary bladder and colon cancer cells. In experiments, Gerner and his colleagues found that tumor cells spread 46 to 62 percent less in a gel matrix over 96 hours when given plecstatin while leaving normal cell function alone, Gerner says
When plectin was immunoprecipitated from the cytoskeletal fractions followed by western blotting, vimentin as well as actin co-immunoprecipitated with plectin (Fig. 2A, lanes 13-18, 31-36), indicating that plectin binds to both vimentin and F-actin in the actin cytoskeleton of invasive bladder cancer YTS-1 and Patient 3 cells Plectin expression was significantly higher in the SW480 colon cancer cell line than the lower grade HT29 colon cancer cell line . In SW480 cells, in vitro suppression of PLEC by siRNA inhibited actin dynamics at scratch wound edges and reduced invasion, migration and adhesion of these cells [ 80 ] When those peptoids were used to pulldown their targets, one of them was identified as plectin, proving that it is a unique biomarker for cancer stem cells. Our studies show both genotypic and.
Recently, in a screen of cell surface markers of pancreatic cancer, we have identified a highly specific and novel cell surface biomarker, Plectin-1. Plectin-1 is normally a cytoplasmic protein predominantly expressed in the muscle and skin. But it is aberrantly surface expressed in in early, precancerous lesions as well as in 100% of human. keywords = drug delivery, non-BRCA mutation, pancreatic cancer, plectin-1 targeting peptide nanoparticles, trap and kill strategy, author = Yazhou Wang and Chong Du and Ying Zhao and Guangjun Nie and Yinmo Yang, note = Funding Information: This work was supported by the Excellent Young Scientists Fund ( 31722021 ), the National Key R&D. IMAGE: University of Houston College of Pharmacy associate professor Gomika Udugamasooriya discovered a new biomarker, plectin, in cancer stem cells that governs cancer survival and spread Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA Integrin α6β4 binds plectin to associate with intermediate filaments such as vimentin. While vimentin and integrin α6β4 are associated with the aggressiveness of triple negative breast cancer (TNBC), the biological importance of their association is not clear. Here, we utilized naturally occurring Epidermolysis. In prostate cancer cells, the downregulation of plectin inhibited cell proliferation, migration, and invasion. The upregulation of plectin positively correlates with the invasion and metastasis of androgen-independent prostate cancer . The findings of Koji et al. indicated that plectin was significantly overexpressed in HNSCC
uPAR, cancer cells can direct the proteolytic activity to the cell surface . As with plectin, the increased ex-pression of uPAR has been linked to the phenomenon epithelial-mesenchymal transition (EMT) [27-29]. In this TMA-based study, low expression of plectin was found to be a marker for a favorable prognosis in non-metastatic OSCC To treat metastatic breast cancer, the study authors suggested, it may be possible to target the RNA splice site that generates the invasion-promoting variant of plectin with small bits of complementary RNA that bind to the splice site sequence and block splicing plectin, a cytolinker protein that mislocalized onto the cell surface during malignant transformation of healthy ovarian tissue. This cancer specific phenotype allowed us to image pancreatic. Plectin-1 as a Novel Biomarker for Pancreatic Cancer. Clinical Cancer Research, 2011. Dirk Bausc
Plectin is an intermediate filament-binding protein that acts as a cross-linking elementin the cytoskeleton. Sequence analysis reveals that plectin is dumbbell shaped and contains a long central α-helical coiled-coil rod flanked by globular domains. Plectinhas six C-terminal repeats that exhibit a tandemly repeated amino acid sequence motif that is characteristic of intermediate filament. To treat metastatic breast cancer, the study authors suggested, it may be possible to target the RNA splice site that generates the invasion-promoting variant of plectin with small bits of complementary RNA that bind to the splice site sequence and block splicing. In the team's experiments, this approach worked to lower the rate of metastasis.
Consistently, plectin knock-down cells have impaired metastatic colonization to distant sites including liver, lung, kidney, bone, and genitourinary system. Plectin knock-down inhibited number of metastases per organ, as well as decreased overall metastatic burden. To gain insights into the role of plectin in prostate cancer growth and. Abstract: Described herein are compositions and methods for cancer cell biomarkers, such as pancreatic ductal adenocarcinoma (PDAC) cell biomarkers, and binding molecules for diagnosis and treatment of cancer, e.g., PDAC. Methods of identifying accessible proteomes are disclosed for identifying cancer biomarkers, such as plectin-1, a PDAC biomarker We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively. For example, plectin has been shown to have a profound impact on cell mechanics [102,103,104], and may directly influence the intrinsic physical properties of the IF network as well. Binding of the 14-3-3 protein to IFs has been shown to alter the intrinsic physical properties of IFs and enhance their softening, leading to the hypothesis of a. Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK has.
Plectin-1 as a novel biomarker for pancreatic cancer Key words Plectin, biomarker, imaging biomarker, pancreatic cancer, PanIN Clinical relevance Specific biomarkers for the detection of pancreatic cancer (PDAC) at an early or preinvasive stage are currently unavailable. Here we report on a pancreatic cancer biomarker, Plectin-1, that. . The purpose of this study was to examine PLEC1 staining in the tumor progression of human colorectal carcinoma. Methods: A tissue microarray of colonic. Plectin-1 is specifically expressed in pancreatic cancer and not in benign inflamedconditions. It is upregulated during carcinogenesis and expressed at high levels in the advanced premetastatic PanIN III lesions. Moreover, a SPECT/CT plectin-1 targeted imaging agent has been developed and validated in numerous stringent mouse models
Plectin is a novel regulator for apical extrusion of RasV12-transformed epithelial cells. To examine the competitive interaction between normal and transformed cells, we have established Madin. Loss or mutations in plectin result in tissue degeneration and loss of cellular structural stability. Plectin depletion reduces the speed, directionality, and persistence of migration, as well as centrosome orientation.18,20 In analogy, plecstatin-1 was shown to exert anti-migratory effects in cancer cell culture models. 10 Moreover, treat Plectin, a linker protein that organizes the cytoskeleton, is critical for cell migration and wound healing. It is specifically expressed in epithelial cells, muscles, and other tissues. Numerous studies have shown that curcumin (diferuloylmethane) has anti-cancer potential. Curcumin can inhibit cancer cell migration and invasion through various signaling pathways Dr. Kelly started the company after discovering, in her lab at UVA in 2008, a protein, called plectin, which is found on the cell surface of certain cancer cells, but not on healthy cells while she was researching pancreatic cancer and has since discovered it in other cancers, such as ovarian, head and neck, and esophageal cancers Plectin is a multifunctional protein that complexes with integrin‐β4 (ITGB4) to form hemidesmosomes, serves as a scaffolding platform crucial to the function of numerous protein signaling pathways and was recently described as an overexpressed protein in pancreatic cancer (Bausch D et al., Clin Cancer Res 2010; Kelly et al., PLoS Med 2008;5.
Plectin knockout (KO) cell lines were generated by targeting genomic sequences of intron 25-26 and exon 31 of Plectin using CRISPR/Cas9 plasmid pX330 Cas9-Venus (a kind gift of B. Schuster, IMG. Her key findings on cancer-specific plectin (CSP) laid the groundwork for her NIH/NCI-funded research efforts to home in on CSP as a strategy to detect pancreatic cancer at its earliest stages. Kelly did not stop at trying to detect pancreatic cancer, however. The ultimate goal is to kill these pancreatic cancer cells
1. Introduction. High-grade serous ovarian cancer (HGSC) is the most lethal gynaecological cancer in the USA .Most patients initially respond to platinum and taxane-based treatments, but subsequently develop chemoresistance; the 5-year survival rate is only 44% .The critical need for successful treatment strategies motivated The Cancer Genome Atlas (TCGA) Network to catalogue the genetic. Plectin is a high molecular mass protein (approx. 500 kDa) with versatile binding properties expressed in almost all cells and tissues. It interacts in vitro with intermediate filament (IF) proteins of various types, including lamins, vimentin, keratins, neurofilaments and GFAP (glial fibrillary acidic protein), and it associates with IFs in cultured cells, as demonstrated by immunoelectron. a mechanism for plectin deregulation in cancer, involving iso- form-speci ﬁ c up-regulation, mislocalization, and extracellular traf ﬁ cking via integrin β 4-binding and exosome secretion Plectin-targeted liposomes enhance the therapeutic efficacy of a PARP inhibitor in the treatment of ovarian cancer. Theranostics. 2018;8(10):2782. Dasa SS, Suzuki R, Gutknecht M, Brinton LT, Tian Y, Michaelsson E, Lindfors L, Klibanov AL, French BA, Kelly KA
The money will fund development of the drug ZB131, which targets a substance Kelly discovered on the surface of many cancer cells, including ovarian, pancreatic, lung and colorectal cancers. Lab work suggests that the drug can bind to the substance, called plectin, stopping the cancer's growth and causing the cells to die Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be. Speciﬁc expression of plectin-1 on pancreatic tumor cells is also the premise for designing plectin-1 targeting nanopar-ticles. Previously, Bausch and colleagues compared the expression of plectin-1 on normal pancreas (n = 4) and pancreatic cancer tissues (n = 41), and they found the high speciﬁcity of plectin-1 on pancreatic cancer tissues. PDF | On Jan 1, 2018, Isao Tamura and others published Expression of Plectin-1 and Trichohyalin in Human Tongue Cancer Cells | Find, read and cite all the research you need on ResearchGat
These screens yielded a tag that distinguishes PDAC cells from normal pancreatic duct cells. As a result of the approach, it was possible to identify a novel biomarker, plectin-1, that may serve as a means for the early detection of pancreatic cancer and confirmation of pancreatic cancer diagnosis BRCA2 interacts with the cytoskeletal linker protein plectin to form a complex controlling centrosome localization Takayoshi Niwa,1,2 Hiroko Saito,2 Shinobu Imajoh-ohmi,3 Michio Kaminishi, 1Yasuyuki Seto, Yoshio Miki2,4,5 and Akira Nakanishi2,3 1Department of Endocrine Surgery and Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo; 2Department of Geneti The C-terminal globular domain of plectin also contains a binding site for vimentin (Castañón et al., 2013). If β4 integrin and vimentin interact with plectin at different ends of the molecule, we would have predicted that β4 integrin and vimentin would be separated by a distance of ∼200 nm
In basal squamous cells, plectin-1 interacts with intermediate filaments, whereas trichohyalin, which is distributed primarily in the medulla and inner root sheath cells of human hair follicles, plays a role in strengthening cells during keratinization. Although both cytoskeletal proteins occur in trace amounts in human tongue epithelial cells, there are minimal data on their expression in. Moreover, in high-metastatic bladder cancer, plectin plays a key role in anchoring invadopodia to IF and in stabilizing invadopodia, which is critical for cancer cell invasion . This all demonstrates plectin's promotion effect on cancer cell migration and cancer progression
Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1 Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells Aaron C. Raymond, Boning Gao , Luc Girard , John D. Minna , D. Gomika Udugamasooriy
Tumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an unbiased peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells. Prostate cancer is a clinically heterogeneous disease, ranging from indolent asymptomatic disease to very aggressive metastatic and life threatening forms of the disease. Distant metastasis represents the major lethal cause of prostate cancer. The most critical clinical challenge in the management of the patients is identifying those individuals at risk of developing metastatic disease Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis. Mihoko Sutoh Yoneyama et al. European journal of cell biology, 93(4), 157-169 (2014-05-09
a mouse orthotopic pancreatic cancer and liver metastasis model. Plectin-1 expression was found to be positive in all pancreatic ductal adenocarcinoma, negative in benign tissue, and increase along the progression of pancreatic cancer. Metastatic deposits in the lymph nodes, liver, and peritoneum were Sensitivity to Her2-directed therapies is complex and involves expression not only of Her2 but also of other epidermal growth factor receptor (EGFR) family members, their ligands, and molecules that influence pathway activity, such as insulin-like growth factor-1 receptor, PTEN, and p27. The EGFR experience has taught us that responses can easily be diluted in an unselected cohort of patients. Aspects of the disclosure provide compositions and methods for treating cancer characterized by surface expression of plectin-1. The disclosure relates, in part, to combinations of therapeutic agents (e.g., anti-plectin-1 antibodies and certain small molecules) that function together (e.g., synergistically) to inhibit cancer cell growth