Suppression of pancreatic cancer growth and metastasis by HMP19 identified through genome-wide shRNA screen.

Abstract:

:Therapeutic effectiveness against metastatic or even locally advanced pancreatic ductal adenocarcinoma (PDAC) is dismal, with 5-year survival less than 5%. Even in patients who undergo potentially curative resection, most patients' tumors recur in the liver. Improving therapies targeting or preventing liver metastases is crucial for improving prognosis. To identify genes suppressing metastasis, a genome-wide shRNA screen was done using the human non-metastatic PDAC cell line, S2-028. After identification of candidates, functional validation was done using intrasplenic and orthotopic injections in athymic mice. HMP19 strongly inhibited metastasis but also partially attenuated tumor growth in the pancreas. Knockdown of HMP19 increased localization of activated ERK1/2 in the nucleus, corresponding to facilitated cell proliferation, decreased p27(Kip1) and increased cyclin E1. Over-expression of HMP19 exerted the opposite effects. Using a tissue microarray of 84 human PDAC, patients with low expression of HMP19 showed significantly higher incidence of liver metastasis (p = 0.0175) and worse prognosis (p = 0.018) after surgery. HMP19, a new metastasis/tumor suppressor in PDAC, appears to alter signaling that leads to cell proliferation and appears to offer prognostic value in human PDAC.

journal_name

Int J Cancer

authors

Kurahara H,Bohl C,Natsugoe S,Nishizono Y,Harihar S,Sharma R,Iwakuma T,Welch DR

doi

10.1002/ijc.30110

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

628-38

issue

3

eissn

0020-7136

issn

1097-0215

journal_volume

139

pub_type

杂志文章
  • The intracellular association of B700 and B50 murine melanoma antigens and their role in tumor rejection.

    abstract::B700 and B50 are melanoma-specific antigens originally isolated from B16 murine melanoma. B700, which elicits a strong tumor rejection response, is present on all murine melanomas tested to date. We now demonstrate the presence of B50 in the other murine melanomas and find that the 2 molecules are non-covalently compl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910430326

    authors: Gersten DM,Williams LJ,Moody D,Montague PM,Law LW,Hearing VJ

    更新日期:1989-03-15 00:00:00

  • Inhibition of a complement regulator in vivo enhances antibody therapy in a model of mammary adenocarcinoma.

    abstract::Membrane-bound complement regulatory proteins provide tumor cells with protection from antibody and complement in vitro. However, complement regulators are widely expressed on normal tissue, and inhibiting the function of complement regulatory proteins on tumor cells in vivo has not been investigated due to the absenc...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20178

    authors: Imai M,Ohta R,Okada N,Tomlinson S

    更新日期:2004-07-20 00:00:00

  • Recombinant feline viruses containing the myc gene rapidly produce clonal tumours expressing T-cell antigen receptor gene transcripts.

    abstract::We, and others, have recently shown that recombinant feline leukaemia viruses (FeLV) containing the myc gene (FeLV-myc) occur in up to 30% of naturally occurring cases of T-cell lymphosarcoma. Investigation of the disease spectrum of two FeLV-myc isolates showed that they induced clonal or oligoclonal T-cell tumours a...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910400108

    authors: Onions D,Lees G,Forrest D,Neil J

    更新日期:1987-07-15 00:00:00

  • Cytoskeleton and ECM tumor mutant peptides: Increased protease sensitivities and potential consequences for the HLA class I mutant epitope reservoir.

    abstract::Cytoskeleton and extracellular matrix-related proteins (CECMPs) represent the most common class of cancer mutants, owing to the large size of their coding regions and the randomness of mutagenesis. We used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to p...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31111

    authors: Callahan BM,Patel JS,Fawcett TJ,Blanck G

    更新日期:2018-03-01 00:00:00

  • Contrasting effects of 17 beta-estradiol on the growth of human ovarian carcinoma cells in vitro and in vivo.

    abstract::A human ovarian adenocarcinoma cell line (PE04) has been established as a xenograft in nude mice. In vitro, this cell line is estrogen receptor (ER)-positive and its growth is stimulated by 17 beta-estradiol at concentrations between 10(-12) and 10(-6) M. When xenografted, PE04 cells remain ER-positive and also posses...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910550323

    authors: Langdon SP,Ritchie A,Young K,Crew AJ,Sweeting V,Bramley T,Hillier S,Hawkins RA,Tesdale AL,Smyth JF

    更新日期:1993-09-30 00:00:00

  • Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic.

    abstract::Sera from 450 individuals between the age of 1 and 80 years, representing the general population of the Czech Republic, were tested for the presence of antibodies to human-papillomavirus(HPV)-derived antigens. The following antigens were used: (i) HPV1 virions; (ii) HPV16, -18 and -33-virus-like particles (VLP); (iii)...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980831)77:5<689::aid-ijc

    authors: Hamsíková E,Ludvíková V,Smahel M,Sapp M,Vonka V

    更新日期:1998-08-31 00:00:00

  • Interleukin-10 production in malignant melanoma: preferential detection of IL-10-secreting tumor cells in metastatic lesions.

    abstract::IL-10 mRNA expression and protein production in established melanoma cell lines and freshly cultured primary and metastatic melanoma cells was examined. The in situ distribution of IL-10 in native melanoma tissue was also investigated by immunohistochemistry in primary tumors, metastases, benign melanocytic nevi and n...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960529)66:5<607::AID-IJC

    authors: Dummer W,Bastian BC,Ernst N,Schänzle C,Schwaaf A,Bröcker EB

    更新日期:1996-05-29 00:00:00

  • Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis.

    abstract::Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29691

    authors: Wangsa D,Chowdhury SA,Ryott M,Gertz EM,Elmberger G,Auer G,Åvall Lundqvist E,Küffer S,Ströbel P,Schäffer AA,Schwartz R,Munck-Wikland E,Ried T,Heselmeyer-Haddad K

    更新日期:2016-01-01 00:00:00

  • Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor.

    abstract::EMT6 is a transplantable mouse mammary tumor cell line that has been utilized widely as a model system to study the effects of various treatments on local tumor growth and pulmonary metastasis. In this study, we examined the cellular mechanisms by which scatter factor (SF), a fibroblast-derived cytokine that stimulate...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910570517

    authors: Rosen EM,Knesel J,Goldberg ID,Jin L,Bhargava M,Joseph A,Zitnik R,Wines J,Kelley M,Rockwell S

    更新日期:1994-06-01 00:00:00

  • Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.

    abstract::Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression o...

    journal_title:International journal of cancer

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/ijc.24506

    authors: Shabo I,Olsson H,Sun XF,Svanvik J

    更新日期:2009-10-15 00:00:00

  • Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer.

    abstract::Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20010601)92:5<671::aid-ijc1240>3

    authors: Seidl J,Rauch J,Krieg RC,Appel S,Baumgartner R,Knuechel R

    更新日期:2001-06-01 00:00:00

  • Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3.

    abstract::Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)-positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The contribution of EBV to the tumor development is not known. Similarly to normal natural killer (NK) cells, cell lines derived from malignancies with a NK phenotype ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22139

    authors: Takahara M,Kis LL,Nagy N,Liu A,Harabuchi Y,Klein G,Klein E

    更新日期:2006-12-15 00:00:00

  • Treatment of AIDS-associated Kaposi's sarcoma in Zimbabwe: results of a randomized quality of life focused clinical trial.

    abstract::Kaposi's sarcoma is currently the most common tumor in Zimbabwe. The purpose of our study is to compare the effectiveness of supportive care vs. 3 intervention approaches, namely oral Etoposide, a 3-drug combination, and radiotherapy using quality of life (QOL) as the primary measure of success. In addition, our study...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/ijc.20606

    authors: Olweny CL,Borok M,Gudza I,Clinch J,Cheang M,Kiire CF,Levy L,Otim-Oyet D,Nyamasve J,Schipper H

    更新日期:2005-02-10 00:00:00

  • Decreased Egr-1 expression in human, mouse and rat mammary cells and tissues correlates with tumor formation.

    abstract::We have examined several types of tumor cell lines and shown that they invariably expressed little or no Egr-1, in contrast to their normal counterparts. We have previously shown that the expression of exogenous Egr-1 in human breast and other tumor cells markedly reduces transformed growth and tumorigenicity. We ther...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970703)72:1<102::aid-ijc

    authors: Huang RP,Fan Y,de Belle I,Niemeyer C,Gottardis MM,Mercola D,Adamson ED

    更新日期:1997-07-03 00:00:00

  • Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma.

    abstract::Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22843

    authors: Dua P,Ingle A,Gude RP

    更新日期:2007-10-01 00:00:00

  • SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II.

    abstract::Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29145

    authors: Choi DS,Stark DJ,Raphael RM,Wen J,Su J,Zhou X,Chang CC,Zu Y

    更新日期:2015-03-01 00:00:00

  • A functional TNFRSF5 polymorphism and risk of non-Hodgkin lymphoma, a pooled analysis.

    abstract::Interaction between CD40 and its ligand, CD154, has a key function in immune regulation. Recent experimental data support a role of deregulated CD40 signalling in lymphomagenesis. Data from earlier studies that are part of this pooling study implicate a functional polymorphism (-1C>T, rs1883832) in the TNFRSF5 gene en...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1002/ijc.25420

    authors: Nieters A,Bracci PM,de Sanjosé S,Becker N,Maynadié M,Benavente Y,Foretova L,Cocco P,Staines A,Holly EA,Boffetta P,Brennan P,Skibola CF

    更新日期:2011-03-15 00:00:00

  • Effect of retinoic acid on bovine papillomavirus (BPV) DNA-induced transformation and number of BPV DNA copies.

    abstract::The effect of all-trans-retinoic acid (RA) was examined on (1) transformation induced in C127 cells by transfection with plasmid pdBPV-1 (142-6), which contains DNA of bovine papillomavirus (BPV), (2) the capacity of transformed BPV DNA-containing clones to form colonies with transformed properties (e.g., piling up in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910420118

    authors: Tsang SS,Li G,Stich HF

    更新日期:1988-07-15 00:00:00

  • Interaction of host and viral risk factors for development of cervical carcinoma in situ.

    abstract::Infection by oncogenic human papillomavirus (HPV) is a necessary but not sufficient cause of cervical carcinoma. Several host genetic and viral factors have been reported to increase the risk of carcinoma development given an HPV infection. In our study, we have analysed the contribution of HPV 16 E6 sequence subtype ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21212

    authors: Beskow AH,Engelmark MT,Magnusson JJ,Gyllensten UB

    更新日期:2005-11-20 00:00:00

  • Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women in cervical screening programs.

    abstract::Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.31261

    authors: Cuschieri K,Ronco G,Lorincz A,Smith L,Ogilvie G,Mirabello L,Carozzi F,Cubie H,Wentzensen N,Snijders P,Arbyn M,Monsonego J,Franceschi S

    更新日期:2018-08-15 00:00:00

  • Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis.

    abstract::EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumor suppressive function in cancer. EPLIN expression was evaluated in prostate can...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31786

    authors: Collins RJ,Morgan LD,Owen S,Ruge F,Jiang WG,Sanders AJ

    更新日期:2018-11-15 00:00:00

  • Expression of the cyclin-dependent kinase inhibitors p16INK4, p15INK4B and p21WAF1/CIP1 in human breast cancer.

    abstract::Aberrant cyclin expression has been implicated in oncogenesis in a number of human cancers. Since altered function of regulators of cyclin-dependent kinase (CDK) activity other than cyclins, in particular CDK inhibitors, might play a similar role in oncogenesis, we examined the expression and regulation of the CDK inh...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910630420

    authors: Musgrove EA,Lilischkis R,Cornish AL,Lee CS,Setlur V,Seshadri R,Sutherland RL

    更新日期:1995-11-15 00:00:00

  • Risks of second primary malignancy in patients with cutaneous and ocular melanoma in Denmark, 1943-1989.

    abstract::Risks of 2nd primary cancer were assessed in all patients with cutaneous melanoma (12,460) and all patients with ocular melanoma (2,018) incident in Denmark from 1943 to 1989 and followed for totals of 88,667 person-years and 16,045 person-years, respectively. After cutaneous melanoma, 972 2nd cancers occurred. The ri...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910610606

    authors: Swerdlow AJ,Storm HH,Sasieni PD

    更新日期:1995-06-09 00:00:00

  • SV-IV, a major protein secreted from rat seminal vesicle epithelium, promotes lymphocyte cytotoxic activity against the lymphoblastoid Raji cell line in human peripheral blood mononuclear cells.

    abstract::The treatment of human peripheral blood mononuclear cells (PBMC) with micromolar concentrations of SV-IV, a major protein secreted from the rat seminal vesicle epithelium, promotes in this cell population a marked cytotoxic activity against the Raji lymphoblastoid cell line. This activity is apparently due to cell-to-...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970717)72:2<321::aid-ijc

    authors: Peluso G,Marchese M,Furgi A,Ranieri M,Russo Spena S,Ravagnan G,Fuggetta MP,Porta R,Metafora V,Metafora S

    更新日期:1997-07-17 00:00:00

  • Genetic polymorphism in the conjugating enzyme UGT1A1 and the risk of head and neck cancer.

    abstract::UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme which catalyses not only the glucuronidation of tobacco smoke carcinogens like benzopyrene, but also of the endogenous substrate bilirubin. Bilirubin for a long time was considered to be only a toxic waste product of hemoglobin degradation, but recent findings have...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25296

    authors: Lacko M,Roelofs HM,Te Morsche RH,Voogd AC,Ophuis MB,Peters WH,Manni JJ

    更新日期:2010-12-15 00:00:00

  • Occurrence of anticancer activity of prednisolone via adrenalectomy and inhibition of adrenaline in rats.

    abstract::In this study, the anticancer effect of prednisolone was investigated using rats with normal endogen adrenaline levels (intact), reduced adrenaline levels (metyrosine-induced) and adrenaline deficiency (adrenalectomized) via gastric adenocarcinoma model. Gastric adenocarcinoma was induced with N-methyl-N'-nitro-N-nitr...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24869

    authors: Suleyman H,Cadirci E,Albayrak A,Halici Z,Gundogdu C,Hacimuftuoglu A

    更新日期:2010-04-01 00:00:00

  • TAp63gamma can substitute for p53 in inducing expression of the maspin tumor suppressor.

    abstract::Maspin is a Class II tumor suppressor protein and plays a role in tumor growth by inhibiting cellular invasion and motility. It is a member of the serpin family of protease inhibitors and has been shown to reduce angiogenesis. Maspin gene expression can be upregulated by the tumor suppressor p53. We tested 7 p53-relat...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20766

    authors: Spiesbach K,Tannapfel A,Mössner J,Engeland K

    更新日期:2005-04-20 00:00:00

  • Beta-galactoside alpha2,6 sialyltransferase in human colon cancer: contribution of multiple transcripts to regulation of enzyme activity and reactivity with Sambucus nigra agglutinin.

    abstract::Colon cancer tissues display an increased activity of beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I) and an increased reactivity with the lectin from Sambucus nigra (SNA), specific for alpha2,6-sialyl-linkages. Experimental and clinical studies indicate a contribution of these alterations to tumor progression,...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20001001)88:1<58::aid-ijc9>3.0.c

    authors: Dall'Olio F,Chiricolo M,Ceccarelli C,Minni F,Marrano D,Santini D

    更新日期:2000-10-01 00:00:00

  • Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis.

    abstract::The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23834

    authors: Ghosh S,Ghosh A,Maiti GP,Alam N,Roy A,Roy B,Roychoudhury S,Panda CK

    更新日期:2008-12-01 00:00:00

  • MKK7 transcription positively or negatively regulated by SP1 and KLF5 depends on HDAC4 activity in glioma.

    abstract::JNK activity has been implicated in the malignant proliferation, invasion and drug-resistance of glioma cells (GCs), but the molecular mechanisms underlying JNK activation are currently unknown. Here, we reported that MKK7, not MKK4, directly activates JNK in GCs and exerts oncogenic effects on tumor formation. Notabl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32321

    authors: Wang Y,Xia Y,Hu K,Zeng M,Zhi C,Lai M,Wu L,Liu S,Zeng S,Huang Z,Ma S,Yuan Z

    更新日期:2019-11-01 00:00:00