Targeted inhibition of dominant PI3-kinase catalytic isoforms increase expression of stem cell genes in glioblastoma cancer stem cell models.

Abstract:

:Cancer stem cells (CSC) exhibit therapy resistance and drive self-renewal of the tumour, making cancer stem cells an important target for therapy. The PI3K signalling pathway has been the focus of considerable research effort, including in glioblastoma (GBM), a cancer that is notoriously resistant to conventional therapy. Different isoforms of the catalytic sub-unit have been associated with proliferation, migration and differentiation in stem cells and cancer stem cells. Blocking these processes in CSC would improve patient outcome. We examined the effect of isoform specific PI3K inhibitors in two models of GBM CSC, an established GBM stem cell line 08/04 and a neurosphere formation model. We identified the dominant catalytic PI3K isoform for each model, and inhibition of the dominant isoform blocked AKT phosphorylation, as did pan-PI3K/mTOR inhibition. Analysis of SOX2, OCT4 and MSI1 expression revealed that inhibition of the dominant p110 subunit increased expression of cancer stem cell genes, while pan-PI3K/mTOR inhibition caused a similar, though not identical, increase in cancer stem cell gene expression. This suggested that PI3K inhibition enhanced, rather than blocked, CSC activity. Careful analysis of the response to specific isoform inhibition will be necessary before specific subunit inhibitors can be successfully deployed against GBM CSC.

journal_name

Int J Oncol

authors

Jones NM,Rowe MR,Shepherd PR,McConnell MJ

doi

10.3892/ijo.2016.3510

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

207-16

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

49

pub_type

杂志文章
  • Characterization of chimeric proteins constructed from human epidermal growth factor (EGF) and the Drosophila EGF-receptor antagonist argos.

    abstract::The Drosophila argos protein is a natural ligand antagonist of Drosophila EGF receptor (DER), but does not interact with the human EGF receptor (EGFR). With a view to generating a corresponding EGFR antagonist, we, have designed five chimeric proteins featuring selected characteristic parts of argos within the framewo...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.10.4.677

    authors: Lohmeyer M,Mason S,Gullick W

    更新日期:1997-04-01 00:00:00

  • miR-19a correlates with poor prognosis of clear cell renal cell carcinoma patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression.

    abstract::MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found t...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3746

    authors: Ma Q,Peng Z,Wang L,Li Y,Wang K,Zheng J,Liang Z,Liu T

    更新日期:2016-12-01 00:00:00

  • Peripheral immunization against malignant rat glioma can induce effective antitumor immunity in the brain.

    abstract::Using two malignant rat glioma cell lines, we tested to what extent peripheral immunization could affect tumor growth in the brain of syngeneic rats. Peripheral subcutaneous (s.c.) immunization was performed with autologous Newcastle-disease-virus (NDV)-infected or non-infected live tumor cells. Thus immunized rats or...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.6.4.759

    authors: Naujocks G,Schmitz A,Schramm J,Wiestler O,Schirrmacher V

    更新日期:1995-04-01 00:00:00

  • SCTR regulates cell cycle-related genes toward anti-proliferation in normal breast cells while having pro-proliferation activity in breast cancer cells.

    abstract::Secretin receptor (SCTR), the G-protein coupled receptor (GPCR) for secretin, has been observed to be upregulated in a few tumor types while downregulated in others, promoting or suppressing the proliferation of tumor cells, respectively. However, little is known about the molecular regulatory mechanism of dysregulati...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2015.3164

    authors: Kang S,Kim B,Kang HS,Jeong G,Bae H,Lee H,Lee S,Kim SJ

    更新日期:2015-11-01 00:00:00

  • Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma.

    abstract::Despite the introduction of 13-cis-retinoic acid (13-cis-RA) into the current chemotherapy, more than half of high-risk neuroblastoma patients have experienced tumor relapses driven by chemoresistant cancer stem cells (CSCs) that can be isolated by their ability to grow as spheres. Although aldehyde dehydrogenase (ALD...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2801

    authors: Hartomo TB,Van Huyen Pham T,Yamamoto N,Hirase S,Hasegawa D,Kosaka Y,Matsuo M,Hayakawa A,Takeshima Y,Iijima K,Nishio H,Nishimura N

    更新日期:2015-03-01 00:00:00

  • Establishment of human fibroma cell lines from a MEN1 patient by introduction of either hTERT or SV40 early region.

    abstract::Establishment of tumor cell lines as model systems for studying tumor biology or as a part of immunotherapeutic anti-cancer strategies is of high importance, whereby the highest possible preservation of the original tumor cell phenotype is a prerequisite for these aims. Since overexpression of the catalytic subunit of...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.26.4.961

    authors: Voglauer R,Grillari J,Fortschegger K,Wieser M,Sterovsky T,Gunsberg P,Katinger H,Pfragner R

    更新日期:2005-04-01 00:00:00

  • Identification and characterization of TMEM24 family genes in silico.

    abstract::MLL gene at human chromosome 11q23.3 is frequently rearranged or amplified in hematological malignancies, while PHLDB1, BCL9L, FOXN5 (FOXR1), RNF26, and MFRP genes linked to MLL gene are deleted in neuroblastoma. Here, we characterized the TMEM24 gene family by using bioinformatics. KIAA0285 gene within the 11q23.3 co...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Katoh M,Katoh M

    更新日期:2004-09-01 00:00:00

  • Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells.

    abstract::Previous investigations have shown that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) have been correlated with the regulation of tumor progression, cellular growth and differentiation in several malignant tumors. The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Nakayama T,Yoshizaki A,Izumida S,Suehiro T,Miura S,Uemura T,Yakata Y,Shichijo K,Yamashita S,Sekin I

    更新日期:2007-04-01 00:00:00

  • Microvessel density predicts the radiosensitivity of metastatic head and neck squamous cell carcinoma in cervical lymph nodes.

    abstract::Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.19.6.1127

    authors: Ito Y,Kamijo T,Yokose T,Kawashima M,Ogino T,Ikeda H,Hayashi R,Sasaki S,Ochiai A

    更新日期:2001-12-01 00:00:00

  • Reliability of a primary culture system to test cytotoxic drug activity in human-malignant melanoma.

    abstract::Optimal conditions have been defined to grow primary cultures of malignant melanoma suitable for in vitro pharmacological studies. A feasibility of primary cultures was observed in 60% of 62 clinical melanoma lymph node metastases. The neoplastic nature of the cells grown in culture, as assessed by the highly specific...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.6.619

    authors: Villa R,Zaffaroni N,Orlandi L,Costa A,Veronese S,Vaglini M,Silvestrini R

    更新日期:1992-11-01 00:00:00

  • Overcoming the classical multidrug resistance phenotype by adenoviral delivery of anti-MDR1 short hairpin RNAs and ribozymes.

    abstract::Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The 'classical' MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kaszubiak A,Holm PS,Lage H

    更新日期:2007-08-01 00:00:00

  • Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo.

    abstract::Meningiomas are the most commonly occurring intracranial tumors and account for approximately 15-20% of central nervous system tumors. Patients whose tumors recur after surgery and radiation therapy have limited therapeutic options. It has also been reported recently that radiation triggers DNA repair, cell survival a...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.934

    authors: Gupta R,Rao Gogineni V,Nalla AK,Chetty C,Klopfenstein JD,Tsung AJ,Mohanam S,Rao JS

    更新日期:2011-04-01 00:00:00

  • Establishment of three malignant peripheral nerve sheath tumor cell lines, FU-SFT8611, 8710 and 9817: conventional and molecular cytogenetic characterization.

    abstract::Malignant peripheral nerve sheath tumor (MPNST) is a rare malignant tumor, for which only a few cultured cell lines are available to date. In the present study, we established three new MPNST cell lines, FU-SFT8611, FU-SFT8710 and FU-SFT9817, from a 40-year-old Japanese man without neurofibromatosis 1 (NF1), a 43-year...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.29.6.1421

    authors: Aoki M,Nabeshima K,Nishio J,Ishiguro M,Fujita C,Koga K,Hamasaki M,Kaneko Y,Iwasaki H

    更新日期:2006-12-01 00:00:00

  • Regulatory effect of the MAFG‑AS1/miR‑150‑5p/MYB axis on the proliferation and migration of breast cancer cells.

    abstract::Long noncoding RNA (lncRNA) MAF BZIP transcription factor G antisense RNA 1 (MAFG‑AS1) has been demonstrated to serve an important role in the progression of various types of cancer, whereas its role in breast cancer has not been fully elucidated. The present study aimed to explore the potential role and underlying me...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5150

    authors: Jia H,Wu D,Zhang Z,Li S

    更新日期:2020-11-20 00:00:00

  • T-cell receptor v-Beta usage of tumor-infiltrating lymphocyte lines cloned from human breast-tumor and melanoma.

    abstract::A total of forty-one tumor infiltrating T cell lines (TIL) were cloned, in the presence of interleukin-2, from nine breast tumor and five melanoma specimens with limiting dilution in a microculture system. Nineteen (46%) of the lines/clones reacted to autologous tumor targets. The T cell receptor (TcR) V beta gene usa...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.7.1.147

    authors: Chin Y,Janssens J,Bleus J,Vandevijver C,Zhang J,Raus J

    更新日期:1995-07-01 00:00:00

  • The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway.

    abstract::The signal transducer and activator of transcription 3 (STAT3) factor plays an important role in the tumorigenicity of cancer stem cells. The purpose of this study was to investigate the inhibitory mechanism of this pathway acting through the tumor suppressor von Hippel-Lindau (VHL) protein in glioma cancer stem cells...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1773

    authors: Kanno H,Sato H,Yokoyama TA,Yoshizumi T,Yamada S

    更新日期:2013-03-01 00:00:00

  • LH-RH receptors in human colorectal cancers: unexpected molecular targets for experimental therapy.

    abstract::Since the efficacy of chemotherapy can be enhanced by targeting to specific receptors on tumors, we investigated the expression of LH-RH receptors in 5 human colon cancer lines and the effects of cytotoxic LH-RH analogs on these tumors. Nude mice bearing HT-29, HCT-116, HCT-15, LoVo and Colo-320DM cancers were treated...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Szepeshazi K,Schally AV,Halmos G

    更新日期:2007-06-01 00:00:00

  • Insights into the distinct roles of MMP-11 in tumor biology and future therapeutics (Review).

    abstract::The biological processes of cancer cells such as tumorigenesis, proliferation, angiogenesis, apoptosis and invasion are greatly influenced by the surrounding microenvironment. The ability of solid malignant tumors to alter the microenvironment represents an important characteristic through which tumor cells are able t...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2016.3400

    authors: Zhang X,Huang S,Guo J,Zhou L,You L,Zhang T,Zhao Y

    更新日期:2016-05-01 00:00:00

  • NLRP3 in human glioma is correlated with increased WHO grade, and regulates cellular proliferation, apoptosis and metastasis via epithelial-mesenchymal transition and the PTEN/AKT signaling pathway.

    abstract::Glioma is the most prevalent and fatal primary tumor of the central nervous system in adults, while the development of effective therapeutic strategies in clinical practice remain a challenge. Nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) has been reported to be associated with tumorigenesis...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4480

    authors: Yin XF,Zhang Q,Chen ZY,Wang HF,Li X,Wang HX,Li HX,Kang CM,Chu S,Li KF,Li Y,Qiu YR

    更新日期:2018-09-01 00:00:00

  • Characterization of side population cells isolated from the colon cancer cell line SW480.

    abstract::Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many types of cell lines and tissues have demonstrated the presence of SP cells, including colon cancer cell lines. This study aimed to identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480. SP c...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2498

    authors: Xiong B,Ma L,Hu X,Zhang C,Cheng Y

    更新日期:2014-09-01 00:00:00

  • The long non‑coding RNA CASC7 inhibits growth and invasion of non‑small cell lung cancer cells through phosphatase and tensin homolog upregulation via sequestration of miR‑92a.

    abstract::Accumulating evidence has demonstrated the crucial roles of long non‑coding RNAs (lncRNAs) in various human cancers, including non‑small cell lung cancer (NSCLC). However, to the best of our knowledge, the role of the lncRNA cancer susceptibility candidate 7 (CASC7) in NSCLC has not been clearly determined. The aim of...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5076

    authors: Chen L,Li X,Lu C,Zhao Y,Zhu J,Yang L

    更新日期:2020-08-01 00:00:00

  • HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo.

    abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000554

    authors: Fiorenzo P,Mongiardi MP,Dimitri D,Cozzolino M,Ferri A,Montano N,Trevisi G,Maira G,Battistini L,Falchetti ML,Levi A,Pallini R

    更新日期:2010-04-01 00:00:00

  • Interleukin-4 inhibits lak and initial phase til activity via interleukin-2 receptor.

    abstract::In the present study, we analyzed the proliferation and cytotoxic activities of LAK cells and initial phase TILs by stimulation with IL-4. IL-4 obviously inhibited the DNA synthesis of LAK cells and initial phase TILs at the concentration of 250 pg/ml and 25 pg/ml, respectively. Furthermore, IL-4 (25 ng/ml for LAK cel...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.7.5.1117

    authors: Tsunoda T,Tanimura H,Yamaue H,Iwahashi M,Tani M,Tamai M,Noguchi K,Mizobata S,Arii K

    更新日期:1995-11-01 00:00:00

  • Effect of cytochrome P450 inducers on expression of oncogenes and a tumor suppressor gene in human colon cancer cells.

    abstract::To examine the possibility that chemical inducers of cytochrome P450 may have effects on the expression of oncogenes and a tumor suppressor gene, human colon LS174T cells were treated with different cytochrome P450 inducers such as benzanthracene (Ba), pyrazole (Pyr) and phenobarbital-hydrocortisone (Pb-Hc). Three for...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.3.427

    authors: Vasquez H,Strobel H

    更新日期:1996-09-01 00:00:00

  • A potential regulatory loop between Lin28B:miR‑212 in androgen-independent prostate cancer.

    abstract::Lin28 is a family of RNA binding proteins and microRNA regulators. Two members of this family have been identified: Lin28A and Lin28B, which are encoded by genes localized in different chromosomes but share a high degree of sequence identity. The role of Lin28B in androgen-independent prostate cancer (AIPC) is not wel...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2647

    authors: Borrego-Diaz E,Powers BC,Azizov V,Lovell S,Reyes R,Chapman B,Tawfik O,McGregor D,Diaz FJ,Wang X,Veldhuizen PV

    更新日期:2014-12-01 00:00:00

  • High expression of ncRAN, a novel non-coding RNA mapped to chromosome 17q25.1, is associated with poor prognosis in neuroblastoma.

    abstract::Neuroblastoma shows complex patterns of genetic aberrations including MYCN amplification, deletion of chromosome 1p or 11q, and gain of chromosome 17q. The 17q gain is frequently observed in high-risk neuroblastomas, however, the candidate genes still remain elusive. In the present study, we integrated the data of com...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000219

    authors: Yu M,Ohira M,Li Y,Niizuma H,Oo ML,Zhu Y,Ozaki T,Isogai E,Nakamura Y,Koda T,Oba S,Yu B,Nakagawara A

    更新日期:2009-04-01 00:00:00

  • Overexpression of lamin B1 induces mitotic catastrophe in colon cancer LoVo cells and is associated with worse clinical outcomes.

    abstract::Lamins are the major components of the nuclear lamina and play important roles in many cellular processes. The role of lamins in cancer development and progression is still unclear but it is known that reduced expression of lamin B1 has been observed in colon cancer. Thus, the aim of the present study was to elucidate...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.4182

    authors: Izdebska M,Gagat M,Grzanka A

    更新日期:2018-01-01 00:00:00

  • High-dose chemotherapy in the treatment of breast-cancer.

    abstract::Dose is a critical determinant of the efficacy of chemotherapy. The dose response curve for virtually all anticancer agents is steep in both in vitro and in vivo experimental studies. However the application of the steep dose-response curve in the clinic has been troublesome for many years because of dose limiting bon...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Honkoop A,Pinedo H

    更新日期:1995-04-01 00:00:00

  • Expression of cell-associated isoform of vascular endothelial growth factor 189 and its prognostic relevance in non-small cell lung cancer.

    abstract::Vascular endothelial growth factor (VEGF) has four isoforms (VEGF121, VEGF165, VEGF189, VEGF206). We examined the expression patterns of VEGF isoforms in non-small cell lung cancer (NSCLC) by RT-PCR. The cell-associated isoform VEGF189 was more frequently expressed in NSCLC (90.5%) than in extraneoplastic lung tissue ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.12.3.541

    authors: Oshika Y,Nakamura M,Tokunaga T,Ozeki Y,Fukushima Y,Hatanaka H,Abe Y,Yamazaki H,Kijima H,Tamaoki N,Ueyama Y

    更新日期:1998-03-01 00:00:00

  • Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin.

    abstract::New drugs that inhibit the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL)/RANK pathway have demonstrated efficacy for the treatment of bone metastasis. Toxicities induced by these drugs, however, including osteonecrosis of the jaw and hypocalcemia, may adversely affect therapy. The aim of this study ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1954

    authors: Uehara H,Takahashi T,Izumi K

    更新日期:2013-08-01 00:00:00