Oncogenic PITX2 facilitates tumor cell drug resistance by inverse regulation of hOCT3/SLC22A3 and ABC drug transporters in colon and kidney cancers.

Abstract:

:Oncogenic pituitary homeobox 2 (PITX2), a de facto master regulator of developmental organ asymmetry, previously upregulated multidrug resistance (MDR) P-glycoprotein ABCB1 in A498 renal cell carcinoma (RCC) cells. The role of PITX2 isoforms in MDR cancers was investigated. Data mining correlated elevated PITX2 in >30% of cancers analyzed, maximally in colon (4.4-fold), confirmed in co-immunostaining of colon and renal cancer microarrays wherein ABCB1 concomitantly increased in RCC. Drug-resistant colorectal adenocarcinoma Colo320DM cells exhibited increased nuclear PITX2 (40-fold), PITX2 promoter activity (27-fold) and ABCB1 (8000-fold) compared to drug-sensitive Colo205. ABCB1 inhibitor PSC833/valspodar or PITX2 siRNA reversed doxorubicin resistance. Nuclei from Colo320DM and A498 cells harbored PITX2A/B1 and PITX2A/B1/B2/Cα/Cβ, respectively. ChIP-qPCR evidenced PITX2 promoter binding in drug exporters ABCB1, ABCC1, ABCG2 and importer hOCT3/SLC22A3. In A498, 786-O, Caki-1, Colo320DM, and Caco2 cells, PITX2 siRNA diminished exporters, increased hOCT3/SLC22A3 expression and activity, and reverted vincristine resistance. Heterologous PITX2 expression induced ABCB1, repressed hOCT3/SLC22A3, enhanced vincristine resistance and diminished proliferation inhibition wherein PITX2A and PITX2C were most effective. Furthermore, PITX2 activity and MDR depended on phosphorylation by GSK3 in A498 cells. Conclusively, oncogenic PITX2 limits sensitizing drug uptake and potentiates cytoprotective drug efflux, contributing to MDR phenotype.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Lee WK,Thévenod F

doi

10.1016/j.canlet.2019.01.044

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

237-251

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30074-6

journal_volume

449

pub_type

杂志文章
  • Acute inhibition of DNA synthesis in hamster buccal pouch epithelium exposed to indirect acting carcinogens.

    abstract::Inhibition of DNA synthesis was observed and quantitated in hamster buccal pouch epithelium exposed in vivo and in vitro to indirect acting carcinogens. Topical application of a 0.5% solution of the potent hamster buccal pouch carcinogen 7,12-dimethylbenz[a]-anthracene (DMBA) acutely inhibited epithelial DNA synthesis...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(90)90210-o

    authors: Nagabhushan M,Ng YK,Elias R,Polverini PJ,Solt DB

    更新日期:1990-09-01 00:00:00

  • Mechanism of uptake of sulfonated metallophthalocyanines by cultured mammalian cells.

    abstract::The uptake of several metallophthalocyanine tetrasulfonates by cultured Chinese hamster cells was studied. Uranyl- and chloraluminium were taken up at the highest rate followed by Ni-, Zn-, Cu-, Co- and dichlorosilicon-phthalocyanine tetrasulfonate. The uptake from the growth medium containing 10% serum in which only ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(87)90217-5

    authors: Ben-Hur E,Siwecki JA,Newman HC,Crane SW,Rosenthal I

    更新日期:1987-12-01 00:00:00

  • Arsenic and chromium enhance transformation of bovine papillomavirus DNA-transfected C3H/10T1/2 cells.

    abstract::Tumor promoters such as phorbol esters, teleocidin and okadaic acid increase the numbers of multilayered, transformed foci produced by BPV DNA-transfected C3H/10T1/2 cells. We questioned whether arsenic and chromium, which are known human carcinogens also enhance transformation of BPV DNA-transfected C3H/10T1/2 cells....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(96)04189-4

    authors: Kowalski LA,Tsang SS,Davison AJ

    更新日期:1996-05-15 00:00:00

  • The inhibitory effects of mangiferin, a naturally occurring glucosylxanthone, in bowel carcinogenesis of male F344 rats.

    abstract::Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside, is one of xanthone derivatives and C-glucosylxanthones, is widely distributed in higher plants and is one of constituents of folk medicines. Recent studies showed that mangiferin has a potential as an anti-oxidant and an anti-viral agent. In this study, we ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00678-9

    authors: Yoshimi N,Matsunaga K,Katayama M,Yamada Y,Kuno T,Qiao Z,Hara A,Yamahara J,Mori H

    更新日期:2001-02-26 00:00:00

  • Tumor exposed-lymphatic endothelial cells promote primary tumor growth via IL6.

    abstract::Solid tumors are composed of tumor cells and stromal cells including lymphatic endothelial cells (LEC), which are mainly viewed as cells forming lymphatic vessels involved in the transport of metastatic and immune cells. We here reveal a new mechanism by which tumor exposed-LEC (teLEC) exert mitogenic effects on tumor...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.10.020

    authors: Van de Velde M,Ebroin M,Durré T,Joiret M,Gillot L,Blacher S,Geris L,Kridelka F,Noel A

    更新日期:2021-01-28 00:00:00

  • Slight promotion effects of intermittent administration of testosterone propionate and/or diethylstilbestrol on 3,2'-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis.

    abstract::In order to determine the effects of intermittent hormonal manipulation on the promotion stage of rat prostate carcinogenesis, testosterone and/or estrogen were administered to F344 rats for 40 weeks after 20-weeks treatment with the prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. For this purpose testosterone pro...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(97)00390-x

    authors: Cui L,Mori T,Takahashi S,Imaida K,Akagi K,Yada H,Yaono M,Shirai T

    更新日期:1998-01-09 00:00:00

  • Increased expression of activated endothelial nitric oxide synthase contributes to antiandrogen resistance in prostate cancer cells by suppressing androgen receptor transactivation.

    abstract::Development of antiandrogen-resistance in advanced prostate cancer involves multiple androgen receptor (AR)-dependent and -independent pathways. Here, we demonstrated that endothelial nitric oxide synthase (eNOS) exhibited an overexpression pattern in hormone-refractory prostate cancer and several models of advanced h...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2012.09.006

    authors: Yu S,Jia L,Zhang Y,Wu D,Xu Z,Ng CF,To KK,Huang Y,Chan FL

    更新日期:2013-01-01 00:00:00

  • Establishment of a new human pancreatic cancer cell line, NOR-P1, with high angiogenic activity and metastatic potential.

    abstract::We present here a new cell line, NOR-P1, established from a metastatic subcutaneous tumor of a patient with pancreatic cancer. The cells show rapid growth in culture with a doubling time of 16 h and high migration activity. Genetic and molecular analyses revealed high telomerase activity and a mutation in the K-ras on...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00421-3

    authors: Sato N,Mizumoto K,Beppu K,Maehara N,Kusumoto M,Nabae T,Morisaki T,Katano M,Tanaka M

    更新日期:2000-07-31 00:00:00

  • Nitric oxide as a target of complementary and alternative medicines to prevent and treat inflammation and cancer.

    abstract::Nitric oxide (NO) and associated reactive nitrogen species (RNS) are involved in many physiological functions. There has been an ongoing debate to whether RNS can inhibit or perpetuate chronic inflammation and associated carcinogenesis. Although the final outcome depends on the genetic make-up of its target, the surro...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2008.03.024

    authors: Hofseth LJ

    更新日期:2008-09-08 00:00:00

  • Differential responses of staurosporine on protein kinase C activity and proliferation in two murine neuroblastoma cell lines.

    abstract::We studied the effect of staurosporine (SSP), a broad-spectrum protein kinase inhibitor, on the levels of protein kinase C (PKC) activity and proliferation in two murine neuroblastoma cell lines, Neuro2a and its clone NB41A3. The PKC activity was examined in whole cell lysate, cytosolic and particulate fractions. A di...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(99)00021-x

    authors: Mohan DR,Nagarathna R,Krishna M,Jagtap JC,Shastry P

    更新日期:1999-05-24 00:00:00

  • Mutagenicity of some congeners of benzidine in the Salmonella typhimurium assay system.

    abstract::The analogs of benzidine were assay for mutagenicity using Salmonella typhimurium TA-98 and TA-100 and a mouse liver enzyme preparation. Only 4-aminobiphenyl produced both frameshift and base pair substitution mutations and 3,3'-dichlorobenzidine was the only compound which was mutagenic without the mammalian enzyme f...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(78)93137-3

    authors: Lazear EJ,Louie SC

    更新日期:1978-01-01 00:00:00

  • Polyphyllin D induces mitochondrial fragmentation and acts directly on the mitochondria to induce apoptosis in drug-resistant HepG2 cells.

    abstract::We previously showed that polyphyllin D (PD) produced a stronger apoptotic effect in R-HepG2 with multi-drug resistance (MDR) than that in its parent HepG2 cells without MDR. In this study, PD was found to elicit mitochondrial fragmentation in live cells by using total internal reflection fluorescence microscopy (TIRF...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2007.11.005

    authors: Ong RC,Lei J,Lee RK,Cheung JY,Fung KP,Lin C,Ho HP,Yu B,Li M,Kong SK

    更新日期:2008-03-18 00:00:00

  • Tumor microenvironment and cancer therapy resistance.

    abstract::Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, however, acquired resistance has emerged as a daunting challenge to anticancer treatments including chemotherapy, radiation and targeted therapy, which abolishes the efficacy of otherwise successful regimens. Cancer cells ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2015.07.044

    authors: Sun Y

    更新日期:2016-09-28 00:00:00

  • TRIP4 promotes tumor growth and metastasis and regulates radiosensitivity of cervical cancer by activating MAPK, PI3K/AKT, and hTERT signaling.

    abstract::Thyroid hormone receptor interactor 4 (TRIP4), a subunit of the tetrameric nuclear activating signal co-integrator 1 (ASC-1) complex, exerts pro-tumorigenic effects. The role for TRIP4 in the regulation of cervical cancer growth and radiation resistance is presently unknown. In this study, TRIP4 was found to be highly...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.03.017

    authors: Che Y,Li Y,Zheng F,Zou K,Li Z,Chen M,Hu S,Tian C,Yu W,Guo W,Luo M,Deng W,Zou L

    更新日期:2019-06-28 00:00:00

  • Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma.

    abstract::We evaluated the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of neuroblastoma cells to cisplatin. Two cell lines, one derived from SH-SY5Y (SY5Y-TB8) and the other from SK-N-AS (AS-TB8), transfected with a TrkB plasmid were generated, and used to assess the effects of activatio...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(02)00723-1

    authors: Jaboin J,Hong A,Kim CJ,Thiele CJ

    更新日期:2003-04-10 00:00:00

  • Increased protein expression of both inducible nitric oxide synthase and cyclooxygenase-2 in human colon cancers.

    abstract::The present study was conducted to investigate protein levels of inducible NO synthase (iNOS) and cayclooxygenase-2 (COX-2) in human colon cancer tissues. Significant increase of iNOS and COX-2 levels in tumors as compared to paired normal tissue was observed in 15 and 28, respectively, of 29 cases investigated. No co...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2005.08.014

    authors: Ohta T,Takahashi M,Ochiai A

    更新日期:2006-08-08 00:00:00

  • Autophagy contributes to the enrichment and survival of colorectal cancer stem cells under oxaliplatin treatment.

    abstract::Currently, chemoresistance is an important cause of treatment failure in colorectal cancer. Cancer stem cells, which are a population of multi-potent cells with the capacity to self-renew and differentiate, have been found to participate in chemoresistance. In the present study, the chemotherapeutic drug oxaliplatin i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2015.02.045

    authors: Yang HZ,Ma Y,Zhou Y,Xu LM,Chen XJ,Ding WB,Zou HB

    更新日期:2015-05-28 00:00:00

  • Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and TRAIL and suppress the growth of H460 human lung cancer cells.

    abstract::Although mesenchymal stem cells (MSCs) have been reported to inhibit tumor growth, the mechanism controlling this tumor suppression function is unclear. Here, we report that high-density (40,000 cells/cm2) cultured adipose tissue-derived MSCs (40K-ASCs) expressed interferon (IFN)-β and tumor necrosis factor-related ap...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2018.10.017

    authors: Jung PY,Ryu H,Rhee KJ,Hwang S,Lee CG,Gwon SY,Kim J,Kim J,Yoo BS,Baik SK,Bae KS,Eom YW

    更新日期:2019-01-01 00:00:00

  • Metabolism of xenobiotics in the human adrenal gland.

    abstract::The capacity of the human adrenal gland to metabolize various xenobiotics was investigated. Adrenal microsomal and mitochondrial preparations showed a maximal absorption at 450 nm for dithionite-reduced cytochromes in the presence of carbon monoxide. Occasionally, absorption maxima at 448 nm were observed with both mi...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(84)90039-9

    authors: Papadopoulos D,Seidegard J,Rydström J

    更新日期:1984-02-01 00:00:00

  • Cloning, sequence analysis and expression of the cDNAs encoding the canine and equine homologues of the mouse double minute 2 (mdm2) proto-oncogene.

    abstract::The mdm2 oncogene is amplified and overexpressed in a variety of human tumours and the oncogenic potential of MDM2 is partly due to its ability to inactivate tumour suppressor p53 function. In the present communication we describe the cloning, sequence analysis and expression of the complete wildtype canine and equine...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(99)00427-9

    authors: Nasir L,Burr PD,McFarlane ST,Gault E,Thompson H,Argyle DJ

    更新日期:2000-04-28 00:00:00

  • Fluoxetine and reversal of multidrug resistance.

    abstract::This review centers on recent findings with respect to modulating cancer multidrug resistance (MDR) with the well-known antidepressant fluoxetine (prozac). The MDR phenomena and mechanisms are discussed, including the roles of ABC transporters as MDR-pumps and the potential involvement of cancer stem cells. The three ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2005.06.003

    authors: Peer D,Margalit R

    更新日期:2006-06-18 00:00:00

  • Inhibitory effects of chlorophyllin on 7,12-dimethylbenz[a]anthracene-induced bacterial mutagenesis and mouse skin carcinogenesis.

    abstract::Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, has been used for the treatment of several abnormal human conditions without apparent toxicity. Recent studies have revealed that CHL has the excellent chemopreventive potential. In the present investigation, we have found the inhibitory activities of CHL...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(99)00229-3

    authors: Chung WY,Lee JM,Park MY,Yook JI,Kim J,Chung AS,Surh YJ,Park KK

    更新日期:1999-10-18 00:00:00

  • Topical inhibition of oral carcinoma cell with polymer delivered celecoxib.

    abstract::Celecoxib has a potential role for oral cancer chemoprevention but its systemic side effects are a concern. Topical chemoprevention is a promising way to reduce the toxicity. This study was designed to determine whether topical application of polymer delivered celecoxib would have an inhibitory effect on human oral ca...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(03)00272-6

    authors: Wang Z,Polavaram R,Shapshay SM

    更新日期:2003-07-30 00:00:00

  • Mutant p53R175H promotes cancer initiation in the pancreas by stabilizing HSP70.

    abstract::Pancreatic cancer remains a highly lethal malignancy. We have recently shown that simultaneous expression of Kras and mutant Tp53R175H promotes invasive ductal adenocarcinoma from pancreatic ductal cells. We hypothesized specific mutations in TP53 have divergent mechanisms of transforming ductal cells. In order to und...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.03.047

    authors: Polireddy K,Singh K,Pruski M,Jones NC,Manisundaram NV,Ponnela P,Ouellette M,Van Buren G,Younes M,Bynon JS,Dar WA,Bailey JM

    更新日期:2019-07-01 00:00:00

  • Tumor-initiating activity of the (+)-(S,S)- and (-)-(R,R)- enantiomers of trans-11,12-dihydroxy-11,12-dihydrodibenzo[a,l]pyrene in mouse skin.

    abstract::A single administration of enantiomerically pure 11,12-dihydrodiols of dibenzo[a,l]pyrene (DB[a,l]P) on the back of NMRI mice and subsequent chronic treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) (initiation/promotion assay) revealed strikingly different carcinogenic activities of both enantiomers. Tumor-in...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(98)00265-1

    authors: Luch A,Friesel H,Seidel A,Platt KL

    更新日期:1999-03-01 00:00:00

  • The glycosylation state of the precursors of the cathepsin B-like proteinase from human malignant ascitic fluid: possible implication in the secretory pathway of these proenzymes.

    abstract::We have investigated the structure of the carbohydrate moiety of the precursors of the cathepsin B-like proteinase (PCBt). The largest precursor has an apparent molecular size (Mr) of 45-47 Kd and it contains 3 N-linked oligosaccharide chains which were Endo beta N acetylglucosaminidase H (Endo H)-resistant forms. On ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(89)90030-x

    authors: Pagano M,Dalet-Fumeron V,Engler R

    更新日期:1989-04-01 00:00:00

  • Detection of a novel lactate dehydrogenase isozyme and an apparent differentiation-associated shift in isozyme profile in hepatoma cell lines.

    abstract::A hitherto unreported lactate dehydrogenase (LD) isoenzyme, which migrates electrophoretically to the relative position between LD2 and LD3 has been identified in the electropheratogram in 7 of 7 (100%) cultured hepatoma cell lines with various degrees of differentiation and is thus given the name LD2-3. LD2-3 seems t...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(94)90222-4

    authors: Liu TZ,Chen PY,Chiu DT,Wei JS,Chang KS,Lin KH

    更新日期:1994-12-09 00:00:00

  • Carcinogenicity examination of quercetin and rutin in ACI rats.

    abstract::Carcinogenicity of quercetin and rutin were examined in inbred ACI strain rats. Rats were given a diet containing 1% or 5% quercetin or 5% rutin for 540 days, or 10% quercetin and 10% rutin for 850 days. Rats in control groups were fed a normal basal diet. Most tumors found in experimental groups were also found in th...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(81)90081-1

    authors: Hirono I,Ueno I,Hosaka S,Takanashi H,Matsushima T,Sugimura T,Natori S

    更新日期:1981-06-01 00:00:00

  • DNA repair of oxidative DNA damage in human carcinogenesis: potential application for cancer risk assessment and prevention.

    abstract::Efficient DNA repair mechanisms comprise a critical component in the protection against human cancer, as indicated by the high predisposition to cancer of individuals with germ-line mutations in DNA repair genes. This includes biallelic germ-line mutations in the MUTYH gene, encoding a DNA glycosylase that is involved...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2008.02.032

    authors: Paz-Elizur T,Sevilya Z,Leitner-Dagan Y,Elinger D,Roisman LC,Livneh Z

    更新日期:2008-07-18 00:00:00

  • Blocking exposed PD-L1 elicited by nanosecond pulsed electric field reverses dysfunction of CD8+ T cells in liver cancer.

    abstract::As a promising method for local tumor treatment, nanosecond pulsed electric field (nsPEF) ablation elicits a potent anti-tumor immune response. However, the mechanism of the nsPEF-mediated anti-tumor immune response and its effects on the tumor microenvironment remains unclear. Here, we demonstrated that nsPEF treatme...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.09.015

    authors: Qian J,Chen T,Wu Q,Zhou L,Zhou W,Wu L,Wang S,Lu J,Wang W,Li D,Xie H,Su R,Guo D,Liu Z,He N,Yin S,Zheng S

    更新日期:2020-12-28 00:00:00