Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance.

Abstract:

:EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways and induce EGFR internalization. This study aims to investigate the role of the EGFR signaling pathway and EGFR internalization in a cetuximab-resistant cell line and to propose a new therapeutic strategy to optimize treatment of HNSCC. The HNSCC cell line, CAL33 was sensitive to gefitinib but resistant to cetuximab. Cetuximab induces an unexpected EGFR phosphorylation in CAL33 cells similarly to EGF but this EGFR activation does not trigger EGFR internalization/degradation, the process currently implicated in the response to cetuximab. Cetuximab inhibits ERK and AKT phosphorylation in cetuximab-sensitive A431 cells, whereas the level of AKT phosphorylation is unmodified in cetuximab-resistant cells. Interestingly, CAL33 cells harbor a PIK3CA mutation. The treatment of CAL33 cells with PI3K inhibitor and cetuximab restores the inhibition of AKT phosphorylation and induces growth inhibition. Our results indicate that EGFR internalization is impaired by cetuximab treatment in CAL33 cells and that the AKT pathway is a central element in cetuximab resistance. The combination of cetuximab with a PI3K inhibitor could be a good therapeutic option in PIK3CA-mutated HNSCC.

journal_name

Int J Oncol

authors

Rebucci M,Peixoto P,Dewitte A,Wattez N,De Nuncques MA,Rezvoy N,Vautravers-Dewas C,Buisine MP,Guerin E,Peyrat JP,Lartigau E,Lansiaux A

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

189-200

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

38

pub_type

杂志文章
  • Ursolic acid promotes colorectal cancer cell apoptosis and inhibits cell proliferation via modulation of multiple signaling pathways.

    abstract::The development of colorectal cancer (CRC) is strongly correlated with the aberrant activation of multiple intracellular signaling transduction cascades including STAT3, ERK, JNK and p38 pathways which usually function redundantly. In addition, crosstalk between these pathways forms a complicated signaling network tha...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.2040

    authors: Lin J,Chen Y,Wei L,Shen A,Sferra TJ,Hong Z,Peng J

    更新日期:2013-10-01 00:00:00

  • Retinoid receptor mRNA expression profiles in human bladder cancer specimens.

    abstract::Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 target genes,...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Boorjian S,Scherr DS,Mongan NP,Zhuang Y,Nanus DM,Gudas LJ

    更新日期:2005-04-01 00:00:00

  • Icariin sensitizes human colon cancer cells to TRAIL‑induced apoptosis via ERK‑mediated upregulation of death receptors.

    abstract::Tumor necrosis factor‑associated apoptosis‑inducing ligand (TRAIL) is considered to be a potential therapeutic target for various types of cancer. However, colon cancer is difficult to treat due to its resistance to TRAIL. Therefore, various trials have been conducted to overcome TRAIL resistance in colon cancer. The ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.4970

    authors: Kim B,Seo JH,Lee KY,Park B

    更新日期:2020-03-01 00:00:00

  • Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma.

    abstract::Hypoxia regulates the expression of genes that promote tumor growth, angiogenesis and invasion. We previously studied hypoxic tumor cells in vitro and from hepatic metastases of colorectal cancer and determined several potential prognostic factors for hepatocellular carcinoma (HCC). In this study, we evaluated the pro...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2519

    authors: Wada H,Yamamoto H,Kim C,Uemura M,Akita H,Tomimaru Y,Hama N,Kawamoto K,Kobayashi S,Eguchi H,Umeshita K,Doki Y,Mori M,Nagano H

    更新日期:2014-09-01 00:00:00

  • Model examination of chemoprevention with retinoids in squamous cell carcinomas of the head and neck region and suitable biomarkers for chemoprevention.

    abstract::The prognosis for patients with head and neck tumors (HNSCC) is poor, due among other things to the high-risk factor for locoregional recurrence and/or second primary tumors. Extensive studies on chemoprevention of oral pre-cancers to stop carcinogenesis and to prevent recurrence and/or second primary tumors have fail...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1139

    authors: Fabricius EM,Kruse-Boitschenko U,Schneeweiss U,Wildner GP,Hoffmeister B,Raguse JD

    更新日期:2011-11-01 00:00:00

  • Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

    abstract::Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The presen...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000701

    authors: Lauriola M,Ugolini G,Rosati G,Zanotti S,Montroni I,Manaresi A,Zattoni D,Rivetti S,Mattei G,Coppola D,Strippoli P,Taffurelli M,Solmi R

    更新日期:2010-08-01 00:00:00

  • Instability and impending instability of the thoracolumbar spine in patients with spinal metastases: a systematic review.

    abstract::Metastatic disease commonly occurs in the spine and incidence is likely to increase secondary to improved survival rates in many cancer patients. Despite published research on instability in patients with metastatic disease of the thoracolumbar spine, controversy exists regarding risk factors for instability and indic...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Weber MH,Burch S,Buckley J,Schmidt MH,Fehlings MG,Vrionis FD,Fisher CG

    更新日期:2011-01-01 00:00:00

  • Establishment of combined immuno-chemotherapy with systemically administered gemcitabine and intra-portal administration of interleukin-2 in murine models of liver metastases of pancreatic cancer.

    abstract::Despite attempts to use multiple drug combinations that include gemcitabine (GEM), there is very little evidence that these combination regimens are superior to the single use of this agent. We therefore investigated the suppressive effect of the combination of systemically administered GEM and locally administered in...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Ito Y,Aiura K,Ueda M,Kitajima M,Kitagawa Y

    更新日期:2008-07-01 00:00:00

  • Gene expression studies of hepatitis virus-induced woodchuck hepatocellular carcinoma in correlation with human results.

    abstract::The lack of good molecular markers for diagnosis as well as treatment assessment has rendered the hepatocellular carcinoma (HCC) a major challenge in health care. In this study, woodchucks were used as an animal model for hepatitis virus-induced HCC, and gene expression studies were performed using a human oligonucleo...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Wang F,Anderson PW,Salem N,Kuang Y,Tennant BC,Lee Z

    更新日期:2007-01-01 00:00:00

  • FAM83A exerts tumor‑suppressive roles in cervical cancer by regulating integrins.

    abstract::Family with sequence similarity 83 member A (FAM83A) has been recently observed to be upregulated in various types of cancer and hypothesized to be serve as an oncogene. The present study aimed to determine the functional roles and the underlying molecular mechanism of FAM83A in cervical cancer. The results demonstrat...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5078

    authors: Xu J,Lu W

    更新日期:2020-08-01 00:00:00

  • Differentiation of human breast carcinoma cells by a novel vitamin D analog: 1alpha-hydroxyvitamin D5.

    abstract::The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3, can induce differentiation in breast cancer cells; however, it is hypercalcemic in vivo. Therefore, development of non-calcemic analogs of vitamin D has received considerable attention. Recently, we synthesized an analog of vitamin D [1alpha(OH)D5] tha...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.16.1.65

    authors: Mehta RR,Bratescu L,Graves JM,Green A,Mehta RG

    更新日期:2000-01-01 00:00:00

  • Phosphoglycerate kinase 1 as a promoter of metastasis in colon cancer.

    abstract::Oxidative stress due to intratumoral hypoxia in solid cancer has been shown to be associated with increased mortality. Phosphoglycerate kinase 1 (PGK1) is an enzyme of the glycolytic pathway, which is regulated by hypoxia-inducible factor-1α (HIF-1α) and has been described for its role in tumor progression and metasta...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1971

    authors: Ahmad SS,Glatzle J,Bajaeifer K,Bühler S,Lehmann T,Königsrainer I,Vollmer JP,Sipos B,Ahmad SS,Northoff H,Königsrainer A,Zieker D

    更新日期:2013-08-01 00:00:00

  • Modulation of Doxorubicin sensitivity and level of p-glycoprotein expression in human colon-carcinoma cells by ectopic and orthotopic environments in nude-mice.

    abstract::The purpose of the study was to determine whether the organ environment can influence the response of colon cancer cells to chemotherapy. The highly metastatic human colon cancer cell line KM12L4, previously selected for production of liver metastases in nude mice, was injected into the cecal wall and into the spleen ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.3.413

    authors: Wilmanns C,Fan D,Obrian C,Radinsky R,Bucana C,Tsan R,Fidler I

    更新日期:1993-09-01 00:00:00

  • Upregulated expression of eIF3C is associated with malignant behavior in renal cell carcinoma.

    abstract::Eukaryotic initiation factor 3c (eIF3C) is involved in the initiation of protein translation. Aberrant eIF3C expression has been reported in different types of human cancer. The present study aimed to assess the role of eIF3C in the malignant behavior of renal cell carcinoma in vitro and in vivo. eIF3C expression was ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2019.4903

    authors: Fan M,Wang K,Wei X,Yao H,Chen Z,He X

    更新日期:2019-12-01 00:00:00

  • Different rates of degradation of the proliferation-associated nuclear and nucleolar antigens during apoptosis of hl-60 cells induced by DNA topoisomerase inhibitors.

    abstract::One of the early events of apoptosis is proteolysis. The enzyme(s) involved in this event appear to be the serine protease(s), inasmuch as the reversible or irreversible inhibitors of serine proteases prevent DNA degradation and abrogate other signs of apoptosis in several cell systems (Gorczyca et al, Int J Oncol 1: ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.4.627

    authors: Gorczyca W,Ardelt B,Darzynkiewicz Z

    更新日期:1993-10-01 00:00:00

  • Reduction of telomeric signals in murine melanoma and human breast cancer cell lines treated with 3'-azido-2'-3'-dideoxythymidine.

    abstract::The purpose of this study was to determine, using fluorescence in situ hybridization (FISH), whether treatment of cancer cells with 3'-azido-2'-3'-dideoxythymidine (AZT) has any effect on telomere length as determined by the telomeric signal intensity. To do so, we treated a metastatic murine melanoma cell line (K-173...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.13.5.923

    authors: Multani AS,Furlong C,Pathak S

    更新日期:1998-11-01 00:00:00

  • Association of rho proteins with the mitochondria organelle.

    abstract::The proteins of the rho gene family have been isolated from cytosolic as well as particulate fractions. The rho proteins have values of about 22KDa and have consensus amino acid sequences for GTP/GDP-binding and GTPase activities. We have localized the rho proteins in mammalian cells by using affinity-purified anti-pe...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.6.1103

    authors: Hauser C,Avraham S,Avraham H

    更新日期:1993-12-01 00:00:00

  • Exosomes released by imatinib‑resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib‑sensitive cells in the presence of imatinib.

    abstract::Chronic myeloid leukemia (CML) is a malignant hematopoietic disorder distinguished by the presence of a BCR‑ABL1 fused oncogene with constitutive kinase activity. Targeted CML therapy by specific tyrosine kinase inhibitors (TKIs) leads to a marked improvement in the survival of the patients and their quality of life. ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5163

    authors: Hrdinova T,Toman O,Dresler J,Klimentova J,Salovska B,Pajer P,Bartos O,Polivkova V,Linhartova J,Machova Polakova K,Kabickova H,Brodska B,Krijt M,Zivny J,Vyoral D,Petrak J

    更新日期:2020-12-23 00:00:00

  • Germline mutation of the PTEN gene in a Japanese patient with Cowden's disease.

    abstract::Cowden's disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN (phosphatase and tensin homologue deleted in chromosome ten) gene has been identified as a tumor suppressor gene responsible for cancers of the endometrium, ovary, prostate, and ...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.18.5.1017

    authors: Kato N,Kimura K,Sugawara H,Aoyagi S,Ikeda T,Horii A

    更新日期:2001-05-01 00:00:00

  • The role of endogenous proteins in the protein-free maintenance of 3 distinct tumor-cell lines invitro.

    abstract::We established new two protein-free culture subclones from murine well-characterized Ehrlich ascites carcinoma and P815 mastocytoma using intermittent protein-free culture performed previously for a protein-free subclone of fibrosarcoma (Gc-4 PF). The Ehrlich protein-free subclone (Ehrlich PF) grew much more slowly th...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.4.481

    authors: Watanabe H,Chigira M

    更新日期:1992-09-01 00:00:00

  • Methylation-related mutations in the BRCA1 promoter in peripheral blood cells from cancer-free women.

    abstract::Early-onset breast cancer is one of the most common malignancies and causes of death among young women, and its incidence is increasing. In the present study, we aimed to investigate the epigenetic modifications of the breast cancer type 1 susceptibility gene (BRCA1) in breast tissues and blood cells derived from wome...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1021

    authors: Al-Moghrabi N,Al-Qasem AJ,Aboussekhra A

    更新日期:2011-07-01 00:00:00

  • Ratio disruption of the ∆133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma.

    abstract::All p53 family members are expressed in several isoforms through alternative promoters and alternative splicing. However, the significance of these isoforms is not yet well understood in cholangiocarcinoma (CCA). In this study, we investigated the expression of p53, p63, p73 and their isoforms at the mRNA and protein ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1818

    authors: Nutthasirikul N,Limpaiboon T,Leelayuwat C,Patrakitkomjorn S,Jearanaikoon P

    更新日期:2013-04-01 00:00:00

  • Autocrine transforming growth factor-alpha is associated with modulation of a 130 kD RB protein species and 116/110 Rb as revealed by an antisense TGF alpha expression vector.

    abstract::Specific RE protein species modulated by autocrine TGF alpha are unknown. HCT116 cells transfected with TGF alpha antisense expression vector were compared with control HCT116 NEO for mitogenesis and modulation of high MW (130, 120 kD) and low MW (116, 110, 105 kD) RE species. Nutrients alone (N) induced maximal mitog...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.8.6.1025

    authors: Dobre C,Ziober B,Humphrey L,Brattain M

    更新日期:1996-06-01 00:00:00

  • Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2.

    abstract::Mutations of p53 tumor suppressor gene increase with tumor progression in colorectal cancers. In this study, we examined the expressions of p33ING1, p14ARF, MDM2 and p21WAF1 mRNA in 25 advanced colorectal cancers by quantitative RT-PCR method, and compared the expression levels of p33ING1, p14ARF, p21WAF1 and MDM2 in ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Tachibana M,Kawamata H,Fujimori T,Omotehara F,Horiuchi H,Ohkura Y,Igarashi S,Kotake K,Kubota K

    更新日期:2004-10-01 00:00:00

  • Enhanced tumorigenic and metastatic potential of an androgen-sensitive human prostate cancer cell line, LNCaP, by intratesticular inoculation in SCID mice.

    abstract::To establish a prostate cancer model expressing prostate-specific antigen (PSA) with metastatic potential, LNCaP or PC-3 cells were inoculated into the testis of SCID mice, resulting in a 100% rate of tumor formation. A significant increase in serum PSA was found in mice with LNCaP xenografts. Circulating tumor cells ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.11.3.513

    authors: Koshida K,Endo Y,Kobayashi T,Imao T,Konaka H,Kadono Y,Uchibayashi T,Sasaki T,Namiki M

    更新日期:1997-09-01 00:00:00

  • Expression of sex-hormone receptors and clinicopathological findings in hepatocellular-carcinoma.

    abstract::We studied the expresssion of estrogen (ER), progesterone (PgR), and androgen receptors (AR) in hepatocellular carcinoma (HCC) and found expression in (7/36), 3.2% (1/31), 16.7% (4/24) of cases, respectively. The expression of ER did not correlate with histological grade, tumor size, or stage of disease. On the other ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.4.6.1349

    authors: Ishizu H,Une Y,Gondo H,Kameda H,Uchino J

    更新日期:1994-06-01 00:00:00

  • Immunomodulation by adriamycin - effect on the production of cytotoxic and inflammatory antitumor immune-responses.

    abstract::We have recently demonstrated in a mouse renal adenocarcinoma tumor system that the antitumor effect of adriamycin (ADM) in combination with interleukin-2 (IL2) is superior to treatment with either ADM or IL2 alone. Based on this observation we postulated that modulation of host's immune competence by ADM and/or IL2 m...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Gautam S,Chikkala N,Ganapathi R

    更新日期:1992-12-01 00:00:00

  • The oncometabolite d‑2‑hydroxyglutarate induces angiogenic activity through the vascular endothelial growth factor receptor 2 signaling pathway.

    abstract::The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d‑ or l‑forms of 2‑hydroxyglutarate (2HG) from α‑ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4649

    authors: Seok J,Yoon SH,Lee SH,Jung JH,Lee YM

    更新日期:2019-02-01 00:00:00

  • Role of nestin expression in angiogenesis and breast cancer progression.

    abstract::Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable mar...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.4223

    authors: Nowak A,Grzegrzółka J,Kmiecik A,Piotrowska A,Matkowski R,Dzięgiel P

    更新日期:2018-02-01 00:00:00

  • Bcl10 expression, rearrangement and mutation in MALT lymphoma: correlation with expression of nuclear factor-kappaB.

    abstract::Mucosa-associated lymphoid tissue (MALT) lymphomas usually involve extranodal sites, especially the stomach, lung and salivary glands. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14) (p22;q32) in MALT lymphomas, and considered to be an apoptosis-associated gene, and involves a caspase recrui...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Ohshima K,Muta H,Kawasaki C,Muta K,Deyev V,Kanda M,Kumano Y,Podack ER,Kikuchi M

    更新日期:2001-08-01 00:00:00