Argininosuccinate lyase interacts with cyclin A2 in cytoplasm and modulates growth of liver tumor cells.

Abstract:

:Arginine is a critical amino acid in specific cancer types including hepatocellular carcinoma (HCC) and melanoma. Novel molecular mechanisms and therapeutic targets in arginine metabolism-mediated cancer formation await further identification. Our laboratory has previously demonstrated that arginine metabolic enzyme argininosuccinate lyase (ASL) promoted HCC formation in part via maintenance of cyclin A2 protein expression and arginine production for channeling to nitric oxide synthase. In this study, we investigated the mechanism by which ASL regulates cyclin A2 expression. We found that ASL interacted with cyclin A2 in HCC cells and the localization of their interaction was in the cytoplasm. Mutation of essential residues for enzymatic activity of ASL did not affect the binding of ASL to cyclin A2. Moreover, the mutant ASL retained the ability to restore the decreased tumorigenicity caused by ASL shRNA. Furthermore, overexpression of ASL conferred resistance to arginine deprivation therapy. Finally, the important pathways and potential therapeutic targets in ASL-regulated HCC were identified by bioinformatics analyses with Metacore database and Connectivity Map database. Our analyses suggested that bisoprolol, celecoxib, and ipratropium bromide, are potential therapeutics for ASL-regulated HCC formation. Thus, ASL interacts with cyclin A2 in cytoplasm, and may promote HCC formation through this non-enzymatic function. Overexpression of ASL may be a contributing factor in drug resistance for arginine deprivation therapy.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Hung YH,Huang HL,Chen WC,Yen MC,Cho CY,Weng TY,Wang CY,Chen YL,Chen LT,Lai MD

doi

10.3892/or.2016.5334

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

969-978

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

37

pub_type

杂志文章
  • Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab‑resistant oral squamous cell carcinoma.

    abstract::High expression of the 110 kDa catalytic subunit of the class IA PI3K (PI3Kp110α) may play an important role in cetuximab resistance exhibited by both colorectal cancer and head and neck squamous cell carcinoma. Therefore, the present study aimed to examine the association between the expression of proteins in the PI3...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7674

    authors: Tsuchihashi H,Naruse T,Yanamoto S,Okuyama K,Furukawa K,Omori K,Umeda M

    更新日期:2020-09-01 00:00:00

  • Natural killer-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia: intracellular cytokine expression and relationship with clinical outcome.

    abstract::The clinical significance of NK-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia (CLL) is still a subject of controversy. There are few previous descriptions that this cell population can be qualitatively or quantitatively deficient in CLL patients. In the present study we investigated the clinical value o...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000924

    authors: Bojarska-Junak A,Hus I,Sieklucka M,Wasik-Szczepanek E,Mazurkiewicz T,Polak P,Dmoszynska A,Rolinski J

    更新日期:2010-09-01 00:00:00

  • Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro.

    abstract::Lapatinib, an inhibitor of human epidermal growth factor receptor 2 (HER2) phosphorylation, has been reported to inhibit several types of tumors such as HER2-overexpressing breast cancer. However, the effect of lapatinib on the malignant phenotype of human osteosarcoma (OS) cells and the potential molecular mechanisms...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2825

    authors: Long XH,Zhang GM,Peng AF,Luo QF,Zhang L,Wen HC,Zhou RP,Gao S,Zhou Y,Liu ZL

    更新日期:2014-01-01 00:00:00

  • Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene.

    abstract::The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4935

    authors: Kong Y,Lu ZL,Wang JJ,Zhou R,Guo J,Liu J,Sun HL,Wang H,Song W,Yang J,Xu HX

    更新日期:2016-09-01 00:00:00

  • Angiogenesis and the immune response as targets for the prevention and treatment of colorectal cancer (review).

    abstract::The carcinogenic process in previously normal human colonic mucosa involves hyperproliferation and adenoma formation, but it is not known why only a tiny proportion of adenomas undergo malignant transformation. There is accumulating evidence in favour of the hypothesis that inflammatory processes are a prerequisite fo...

    journal_title:Oncology reports

    pub_type: 杂志文章,评审

    doi:

    authors: Sharma RA,Dalgleish AG,Steward WP,O'Byrne KJ

    更新日期:2003-09-01 00:00:00

  • The role of photosensitized macrophages in photodynamic therapy.

    abstract::Cancer stimulates macrophage infiltration and encourages angiogenesis, which is necessary for tumor growth and invasion. It seems, that the influence of photodynamic therapy (PDT) on immune cells and immune regulators plays a crucial role in this process. In order to study this effect, the influence of δ-aminolevulini...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1262

    authors: Kawczyk-Krupka A,Czuba Z,Szliszka E,Król W,Sieroń A

    更新日期:2011-07-01 00:00:00

  • Accuracy of criteria for predicting recurrence and metastasis in stage II and III gastric cancer patients with lymph node metastasis.

    abstract::This study assessed the prediction of gastric cancer recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes, and by using criteria that were developed to identify patients with a high risk of recurrence/metastasis. The subjects were 60 patients of stage II or III gastric cancer with lymph node ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Mukai M,Sato S,Komatsu N,Kimura T,Ninomiya H,Kawada M,Nakasaki H,Ogoshi K,Makuuchi H

    更新日期:2004-07-01 00:00:00

  • The role of heparanase in gastrointestinal cancer (Review).

    abstract::Heparanase is endoglycosidase that degrades heparan sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Heparanase has been thought to have an important role in the process of cancer invasion and metastasis. Recent studies have revealed that heparanase has multifunctional mo...

    journal_title:Oncology reports

    pub_type: 杂志文章,评审

    doi:

    authors: Naomoto Y,Takaoka M,Okawa T,Nobuhisa T,Gunduz M,Tanaka N

    更新日期:2005-07-01 00:00:00

  • Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway.

    abstract::The model animal of renal cell carcinoma (RCC), the Eker rat, has a germline mutation in the tuberous sclerosis 2 (Tsc2) gene. Heterozygous mutants develop RCCs by second hit in the wild-type Tsc2 allele, whereas homozygous mutants are embryonic lethal. In the present study, a new cell differentiation model was develo...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4254

    authors: Kawano H,Ito Y,Kanai F,Nakamura E,Tada N,Takai S,Horie S,Kobayashi T,Hino O

    更新日期:2015-11-01 00:00:00

  • Knockdown of CXCR7 inhibits proliferation and invasion of osteosarcoma cells through inhibition of the PI3K/Akt and β-arrestin pathways.

    abstract::CXC chemokine receptor 7 (CXCR7) has been implicated in tumor development and metastasis in multiple malignancies. Yet, the function and molecular mechanisms of CXCR7 in human osteosarcoma (OS) are still unclear. The aim of the present study was to investigate the role of CXCR7 in human OS. The expression of CXCR7 was...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3290

    authors: Zhang Y,Yang CQ,Gao Y,Wang C,Zhang CL,Zhou XH

    更新日期:2014-09-01 00:00:00

  • Leukemia inhibitory factor receptor negatively regulates the metastasis of pancreatic cancer cells in vitro and in vivo.

    abstract::Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Frequent metastasis and recurrence are the main reasons for the poor prognosis of PC patients. Thus, the discovery of new biomarkers and wider insights into the mechanisms involved in pancreatic tumorigenesis and metastasis is cruc...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4865

    authors: Ma D,Jing X,Shen B,Liu X,Cheng X,Wang B,Fu Z,Peng C,Qiu W

    更新日期:2016-08-01 00:00:00

  • Contrasting effects of extended low dose versus standard dose shorter course UFT chemotherapy on microscopic versus macroscopic established tumors: implications for optimal postoperative adjuvant chemotherapy.

    abstract::Given such differences as relative tumor burden, the optimal dose and schedule for postoperative adjuvant chemotherapy of microscopic disease might be expected to differ significantly from therapy of advanced higher volume disease. We investigated this hypothesis by determining the optimal dose and schedule of the 5-F...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Uchida J,Okabe H,Nakano K,Fujioka A,Saito H,Sugimoto Y,Oka T,Fukushima M

    更新日期:2007-08-01 00:00:00

  • Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation.

    abstract::The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells b...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5587

    authors: Yasui H,Ohnishi Y,Nakajima M,Nozaki M

    更新日期:2017-06-01 00:00:00

  • GLIS2 redundancy causes chemoresistance and poor prognosis of gastric cancer based on co‑expression network analysis.

    abstract::Gastric cancer is currently the fourth most common cancer and the third leading cause of cancer‑associated mortality worldwide. Studies have identified that certain biomarkers contribute to the prognosis, diagnosis and treatment of gastric cancer. However, the biomarkers of gastric cancer are rarely used clinically. T...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6794

    authors: Yuan J,Tan L,Yin Z,Tao K,Wang G,Shi W,Gao J

    更新日期:2019-01-01 00:00:00

  • Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma.

    abstract::Hypoxia promotes the invasive and metastatic potential of tumour cells. A recent study has shown that the activation of the chemokine receptor CXCR4 by lack of oxygen in breast cancer is HIF-1-dependent. We have previously demonstrated that CXCR4 signalling is involved in the establishment of lymph node metastasis in ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Ishikawa T,Nakashiro K,Klosek SK,Goda H,Hara S,Uchida D,Hamakawa H

    更新日期:2009-03-01 00:00:00

  • Effect of PPM1H on malignant phenotype of human pancreatic cancer cells.

    abstract::The objective of this study was to investigate the effect of silencing gene protein phosphatase 1H (PPM1H) on malignant phenotype of human pancreatic cancer cell line BxPC-3. In order to explore the function of PPM1H in pancreatic cancer cells, real-time PCR and western blotting were used to detect the expression of P...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5065

    authors: Zhu H,Qin H,Li DM,Liu J,Zhao Q

    更新日期:2016-11-01 00:00:00

  • Paclitaxel enhances tumoricidal potential of TRAIL via inhibition of MAPK in resistant gastric cancer cells.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy due to its unique capacity to selectively trigger apoptosis in cancer cells. However, TRAIL therapy is greatly hampered by its resistance. A preclinical successful strategy is to identify combination treatments that sensit...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4666

    authors: Li L,Wen XZ,Bu ZD,Cheng XJ,Xing XF,Wang XH,Zhang LH,Guo T,Du H,Hu Y,Fan B,Ji JF

    更新日期:2016-05-01 00:00:00

  • ARC is highly expressed in nasopharyngeal carcinoma and confers X-radiation and cisplatin resistance.

    abstract::Apoptosis repressor with caspase recruitment domain (ARC), an inhibitor of apoptosis, is primarily expressed in terminally differentiated tissues. Recent studies have revealed that ARC is highly expressed in a variety of human cancer cell lines and epithelial-derived cancers, which suggests that ARC plays an important...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2622

    authors: Wu P,Tang Y,He J,Qi L,Jiang W,Zhao S

    更新日期:2013-10-01 00:00:00

  • miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes.

    abstract::Accumulating evidence has shown that aberrantly expressed microRNAs (miRNAs) are associated with tumor development and progression. Our previous study found that microRNA-375 (miR-375) was downregulated in colorectal cancer (CRC), but little is known concerning the role of miR-375 and the related mechanism in CRC deve...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4834

    authors: Cui F,Wang S,Lao I,Zhou C,Kong H,Bayaxi N,Li J,Chen Q,Zhu T,Zhu H

    更新日期:2016-07-01 00:00:00

  • Curcumin induces apoptosis through FAS and FADD, in caspase-3-dependent and -independent pathways in the N18 mouse-rat hybrid retina ganglion cells.

    abstract::Curcumin, a naturally occurring yellow pigment isolated from turmeric, is a well known antioxidant with broad spectrum of anti-tumor activities against many human cancer cells. In this study, curcumin-induced cytotoxic effect of mouse-rat hybrid retina ganglion cells (N18) were investigated. For determining cell viabi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000411

    authors: Lu HF,Lai KC,Hsu SC,Lin HJ,Yang MD,Chen YL,Fan MJ,Yang JS,Cheng PY,Kuo CL,Chung JG

    更新日期:2009-07-01 00:00:00

  • ERK/GSK3β signaling is involved in atractylenolide I-induced apoptosis and cell cycle arrest in melanoma cells.

    abstract::Novel agents need to be developed to overcome the limitations of the current melanoma therapeutics. Atractylenolide I (AT-I) is a sesquiterpene compound isolated from atractylodis macrocephalae rhizoma. Previous findings demonstrated that AT-I exhibited cytotoxic action in melanoma cells. However, the molecular mechan...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4111

    authors: Ye Y,Chao XJ,Wu JF,Cheng BC,Su T,Fu XQ,Li T,Guo H,Tse AK,Kwan HY,Du J,Chou GX,Yu ZL

    更新日期:2015-09-01 00:00:00

  • Alterations of the K-ras and p53 genes in Tamoxifen-associated endometrial carcinoma.

    abstract::To better understand the molecular mechanisms of carcinogenesis induced in uterine endometrium by therapeutic anti-estrogenic Tamoxifen (TAM) exposure, 27 uterine tumors (4 benign endometrial polyps and 23 carcinomas) associated with TAM exposure were analyzed for the presence and spectrum of p53 and K-ras mutations. ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Fujiwara K,Enomoto T,Fujita M,Kanda T,Fujii S,Ito K,Wakasa K,Ishiko O,Ueda M,Yamaguchi S,Kimura T,Umesaki N

    更新日期:2008-05-01 00:00:00

  • An eight-long non-coding RNA signature as a candidate prognostic biomarker for lung cancer.

    abstract::Cumulative evidence suggests that long non-coding RNAs (lncRNAs) may be good biomarkers in various types of tumors. In the present study, we mined lncRNA expression profiling in 739 lung cancer patients from Gene Expression Omnibus (GEO) datasets. A risk score model was constructed based on the expression data of thes...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4817

    authors: Tu Z,He D,Deng X,Xiong M,Huang X,Li X,Hao L,Ding Q,Zhang Q

    更新日期:2016-07-01 00:00:00

  • DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma.

    abstract::DNA methylation plays an important role in the genesis and progression of tumor diseases. To identify new DNA methylation markers possibly associated with the clinical characteristics of renal cell carcinoma (RCC), we investigated loci in the sarcosine dehydrogenase (SARDH) gene. SARDH is involved in the metabolism of...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7305

    authors: Mazdak M,Tezval H,Callauch JC,Dubrowinskaja N,Peters I,Bokemeyer C,Hennenlotter J,Stenzl A,Kuczyk MA,Serth J

    更新日期:2019-11-01 00:00:00

  • Perillyl alcohol causes G1 arrest through p15(INK4b) and p21(WAF1/Cip1) induction.

    abstract::The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and is currently being tested in clinical trials in patients with refractory advanced cancers. POH inhibits...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2167

    authors: Koyama M,Sowa Y,Hitomi T,Iizumi Y,Watanabe M,Taniguchi T,Ichikawa M,Sakai T

    更新日期:2013-02-01 00:00:00

  • Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases.

    abstract::To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC)...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yoshimoto A,Kasahara K,Kawashima A,Fujimura M,Nakao S

    更新日期:2005-06-01 00:00:00

  • Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation.

    abstract::Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80‑90% of skin‑cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6356

    authors: Wei C,Lu N,Wang L,Zhang Y,Feng Z,Yang Y,Qi F,Gu J

    更新日期:2018-06-01 00:00:00

  • CHAF1B promotes proliferation and reduces apoptosis in 95‑D lung cancer cells and predicts a poor prognosis in non‑small cell lung cancer.

    abstract::Chromatin assembly factor 1 subunit B (CHAF1B) participates in DNA synthesis and repair. High CHAF1B expression has been associated with a poor prognosis in several types of cancers. However, no study has evaluated the clinical significance and biological function of CHAF1B in non‑small cell lung cancer (NSCLC). In th...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.6994

    authors: Duan Y,Liu T,Li S,Huang M,Li X,Zhao H,Li J

    更新日期:2019-04-01 00:00:00

  • Cetuximab-mediated ADCC activity is correlated with the cell surface expression level of EGFR but not with the KRAS/BRAF mutational status in colorectal cancer.

    abstract::Cetuximab, an IgG1 monoclonal antibody against the epidermal growth factor receptor (EGFR), is widely used for the treatment of metastatic colorectal cancer (mCRC). One of the mechanisms of action is considered to be antibody-dependent cell-mediated cytotoxicity (ADCC) triggered by Fcγ-R on natural killer cells. Howev...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3077

    authors: Seo Y,Ishii Y,Ochiai H,Fukuda K,Akimoto S,Hayashida T,Okabayashi K,Tsuruta M,Hasegawa H,Kitagawa Y

    更新日期:2014-05-01 00:00:00

  • Fusion induced reversal of dendritic cell maturation: an altered expression of inflammatory chemokine and chemokine receptors in dendritomas.

    abstract::Dendritic cell-mediated cancer immunotherapy employs several ways to engage tumor antigens. We have demonstrated in both pre-clinical animal studies and early clinical trials that dendritomas, highly purified hybrids between dendritic cells (DC) and tumor cells, are superior activators of anti-tumor immunity. It has b...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Branham-O'Connor M,Li J,Kotturi HS,Yu X,Wagner TE,Wei Y

    更新日期:2010-02-01 00:00:00