Combination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells.


:The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic options for BRAFi-R melanoma patients. We confirmed the development of BRAFi resistance in our BRAFi-treated melanoma cell lines by demonstrating reduced sensitivity to BRAF inhibitors, increased ERK1/2 activity and increased WNT5A expression. Here, we demonstrated for the first time that high secretion of interleukin-6 (IL-6) was associated with increased invasive migration of BRAFi-R melanoma cells. This finding could be readily explained by the increased expression of WNT5A in BRAFi-R melanoma cells and the presence of an IL-6/WNT5A positive feedback loop in parental melanoma cells. Surprisingly, however, we found that the IL-6/WNT5A positive feedback loop present in parental melanoma cells was lost during the development of acquired BRAFi resistance, meaning that IL-6 and WNT5A signalling were independent events in BRAFi-R melanoma cells. Despite the absence of an IL-6/WNT5A loop, we found that both an IL-6 blocking antibody and the WNT5A antagonist Box5 alone impaired the elevated invasive migration of BRAFi-R melanoma cells, but combined use of the two was more effective. This impaired invasive migration of BRAFi-R melanoma cells correlated well with the reduction in Cdc42-GTPase activity and alterations of the actin cytoskeleton in these cells. In summary, our novel identification of IL-6 as a key independent promoter of the invasive migration of BRAFi-R melanoma cells stresses that a combination of a blocking IL-6 antibody and administration of the WNT5A antagonist Box5 might be an attractive antimetastatic approach for future treatment of BRAFi-R melanoma patients.


Mol Oncol


Molecular oncology


Mohapatra P,Prasad CP,Andersson T




Has Abstract


2019-02-01 00:00:00












  • A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis.

    abstract::We have recently gained a remarkable understanding of the mutational landscape of head and neck squamous cell carcinoma (HNSCC). However, the nature of the dysregulated signaling networks contributing to HNSCC progression is still poorly defined. Here, we have focused on the role of the family of mitogen activated kin...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Leelahavanichkul K,Amornphimoltham P,Molinolo AA,Basile JR,Koontongkaew S,Gutkind JS

    更新日期:2014-02-01 00:00:00

  • The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe.

    abstract::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Drápela S,Khirsariya P,van Weerden WM,Fedr R,Suchánková T,Búzová D,Červený J,Hampl A,Puhr M,Watson WR,Culig Z,Krejčí L,Paruch K,Souček K

    更新日期:2020-10-01 00:00:00

  • Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis.

    abstract::Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alte...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Balaban S,Lee LS,Varney B,Aishah A,Gao Q,Shearer RF,Saunders DN,Grewal T,Hoy AJ

    更新日期:2018-09-01 00:00:00

  • Efficacy of nano-particulated, water-soluble erlotinib against intracranial metastases of EGFR-mutant lung cancer.

    abstract::Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)-mutant lung cancer, which arises due to poor penetration of the brain-blood barrier by EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although osimertinib, a third-generation EGFR-TKI, has efficacy agai...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Kim DH,Choi YJ,Sung KJ,Yoo SA,Sung YH,Kim JK,Choi CM,Yun M,Lee EY,Jin YS,Cook S,Rho JK,Lee JC

    更新日期:2018-12-01 00:00:00

  • Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity in lung cancer cells.

    abstract::Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expres...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Vaughan CA,Singh S,Grossman SR,Windle B,Deb SP,Deb S

    更新日期:2017-06-01 00:00:00

  • Circulating tumor cell detection and single-cell analysis using an integrated workflow based on ChimeraX® -i120 Platform: A prospective study.

    abstract::Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX® -i120 platform to facilitate negative enrichment, immunofluorescent labelin...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Wang PX,Sun YF,Jin WX,Cheng JW,Peng HX,Xu Y,Zhou KQ,Chen LM,Huang K,Wu SY,Hu B,Zhang ZF,Guo W,Cao Y,Zhou J,Fan J,Yang XR

    更新日期:2020-12-10 00:00:00

  • Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR-expressing non-small cell lung cancer to EGFR TKIs.

    abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Tu CY,Cheng FJ,Chen CM,Wang SL,Hsiao YC,Chen CH,Hsia TC,He YH,Wang BW,Hsieh IS,Yeh YL,Tang CH,Chen YJ,Huang WC

    更新日期:2018-05-01 00:00:00

  • DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables.

    abstract::The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Kamalakaran S,Varadan V,Giercksky Russnes HE,Levy D,Kendall J,Janevski A,Riggs M,Banerjee N,Synnestvedt M,Schlichting E,Kåresen R,Shama Prasada K,Rotti H,Rao R,Rao L,Eric Tang MH,Satyamoorthy K,Lucito R,Wigler M,Dim

    更新日期:2011-02-01 00:00:00

  • Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.

    abstract::Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated ...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Deva Magendhra Rao AK,Patel K,Korivi Jyothiraj S,Meenakumari B,Sundersingh S,Sridevi V,Rajkumar T,Pandey A,Chatterjee A,Gowda H,Mani S

    更新日期:2019-06-01 00:00:00

  • The epigenetics of breast cancer.

    abstract::Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by se...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审


    authors: Jovanovic J,Rønneberg JA,Tost J,Kristensen V

    更新日期:2010-06-01 00:00:00

  • Glycan-related gene expression signatures in breast cancer subtypes; relation to survival.

    abstract::Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their ...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Potapenko IO,Lüders T,Russnes HG,Helland Å,Sørlie T,Kristensen VN,Nord S,Lingjærde OC,Børresen-Dale AL,Haakensen VD

    更新日期:2015-04-01 00:00:00

  • Quality-assured research environments for translational cancer research.

    abstract::In order to secure high-quality cancer care for increasing numbers of cancer patients in the upcoming decades, the complete continuum of cancer research and cancer care needs a thorough overhaul, with more emphasis on prevention and early detection, and a greater focus on the development of innovative treatments that ...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审


    authors: Berns A

    更新日期:2019-03-01 00:00:00

  • Discovery and validation of extracellular vesicle-associated miRNAs as noninvasive detection biomarkers for early-stage non-small-cell lung cancer.

    abstract::miRNAs in circulating extracellular vesicles (EVs) are promising biomarkers for cancer. However, their diagnostic ability for early-stage non-small-cell lung cancer (NSCLC) is not well known. In this study, the circulating EV miRNAs profiling was initially performed in 36 untreated NSCLC patients and 36 healthy contro...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Zhong Y,Ding X,Bian Y,Wang J,Zhou W,Wang X,Li P,Shen Y,Wang JJ,Li J,Zhang C,Wang C

    更新日期:2020-12-19 00:00:00

  • Programmed death-ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21-gene and 70-gene signatures in estrogen receptor-positive disease.

    abstract::Gene and protein expression of programmed death-ligand 1 (PD-L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)-related g...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Zerdes I,Sifakis EG,Matikas A,Chrétien S,Tobin NP,Hartman J,Rassidakis GZ,Bergh J,Foukakis T

    更新日期:2020-05-01 00:00:00

  • Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients.

    abstract::Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called 'liquid biopsy' can be applied to monitor response...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审


    authors: Siravegna G,Bardelli A

    更新日期:2016-03-01 00:00:00

  • Pharmacologic inhibition of Akt in combination with chemotherapeutic agents effectively induces apoptosis in ovarian and endometrial cancer cell lines.

    abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Fabi F,Adam P,Parent S,Tardif L,Cadrin M,Asselin E

    更新日期:2020-12-18 00:00:00

  • A report from a conference jointly organised by the European Academy of Cancer Sciences and the Pontifical Academy of Sciences, The Vatican, November 16-17, 2018.

    abstract::Cancer is a massive challenge with a significant impact on society, healthcare systems, the economy and an increasing number of patients and their families. To help meet this societal challenge, the European Commission has recently proposed a mission-oriented approach to cancer in Horizon Europe, and about 60 particip...

    journal_title:Molecular oncology



    authors: European Academy of Cancer Sciences.

    更新日期:2019-03-01 00:00:00

  • The interaction of PKN3 with RhoC promotes malignant growth.

    abstract::PKN3 is an AGC-family protein kinase implicated in growth of metastatic prostate cancer cells with phosphoinositide 3-kinase pathway deregulation. The molecular mechanism, however, by which PKN3 contributes to malignant growth and tumorigenesis is not well understood. Using orthotopic mouse tumor models, we now show t...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Unsal-Kacmaz K,Ragunathan S,Rosfjord E,Dann S,Upeslacis E,Grillo M,Hernandez R,Mack F,Klippel A

    更新日期:2012-06-01 00:00:00

  • Interaction of transcription factor AP-2 gamma with proto-oncogene PELP1 promotes tumorigenesis by enhancing RET signaling.

    abstract::A significant proportion of estrogen receptor-positive (ER+) breast cancer (BC) initially responds to endocrine therapy but eventually evolves into therapy-resistant BC. Transcription factor AP-2 gamma (TFAP2C) is a known regulator of ER activity, and high expression of TFAP2C is associated with a decreased response t...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Liu J,Liu Z,Li M,Tang W,Pratap UP,Luo Y,Altwegg KA,Li X,Zou Y,Zhu H,Sareddy GR,Viswanadhapalli S,Vadlamudi RK

    更新日期:2020-12-02 00:00:00

  • Clinical implications of plasma circulating tumor DNA in gynecologic cancer patients.

    abstract::Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next-generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real-time representation of a tumor and its molecular heterogeneity than tissue. Howe...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Charo LM,Eskander RN,Okamura R,Patel SP,Nikanjam M,Lanman RB,Piccioni DE,Kato S,McHale MT,Kurzrock R

    更新日期:2021-01-01 00:00:00

  • MicroRNA let-7b regulates genomic balance by targeting Aurora B kinase.

    abstract::The let-7 microRNA (miRNA) family has been implicated in the regulation of diverse cellular processes and disease pathogenesis. In cancer, loss-of-function of let-7 miRNAs has been linked to tumorigenesis via increased expression of target oncogenes. Excessive proliferation rate of tumor cells is often associated with...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Mäki-Jouppila JH,Pruikkonen S,Tambe MB,Aure MR,Halonen T,Salmela AL,Laine L,Børresen-Dale AL,Kallio MJ

    更新日期:2015-06-01 00:00:00

  • Epigenetic-smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients.

    abstract::Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylatio...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Ji X,Lin L,Shen S,Dong X,Chen C,Li Y,Zhu Y,Huang H,Chen J,Chen X,Wei L,He J,Duan W,Su L,Jiang Y,Fan J,Guan J,You D,Shafer A,Bjaanæs MM,Karlsson A,Planck M,Staaf J,Helland Å,Esteller M,Wei Y,Zhang R,C

    更新日期:2020-11-01 00:00:00

  • TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.

    abstract::cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Gymnopoulos M,Betancourt O,Blot V,Fujita R,Galvan D,Lieuw V,Nguyen S,Snedden J,Stewart C,Villicana J,Wojciak J,Wong E,Pardo R,Patel N,D'Hooge F,Vijayakrishnan B,Barry C,Hartley JA,Howard PW,Newman R,Coronella J

    更新日期:2020-01-01 00:00:00

  • FOXA1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome.

    abstract::Estrogen receptor-alpha (ERα)-positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERα activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERα-chromatin binding and are crucial for ERα-dr...

    journal_title:Molecular oncology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Schrijver W,Schuurman K,van Rossum A,Droog M,Jeronimo C,Salta S,Henrique R,Wesseling J,Moelans C,Linn SC,van den Heuvel M,van Diest P,Zwart W

    更新日期:2018-11-01 00:00:00

  • Neurotensin signaling induces intracellular alkalinization and interleukin-8 expression in human pancreatic cancer cells.

    abstract::Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer ce...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Olszewski U,Hamilton G

    更新日期:2009-06-01 00:00:00

  • The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex.

    abstract::Recently, RNAs interacting with proteins have been implicated in playing an important role in the occurrence and progression of oesophageal squamous cell carcinoma (ESCC). In this study, we found that NELFA mRNA interacts with Rad17 through a novel noncoding mode in the nucleus and that the aberrant expression of USF2...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Xu J,Wang G,Gong W,Guo S,Li D,Zhan Q

    更新日期:2020-03-01 00:00:00

  • Differential expression of miRNAs in pancreatobiliary type of periampullary adenocarcinoma and its associated stroma.

    abstract::Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are kno...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Sandhu V,Bowitz Lothe IM,Labori KJ,Skrede ML,Hamfjord J,Dalsgaard AM,Buanes T,Dube G,Kale MM,Sawant S,Kulkarni-Kale U,Børresen-Dale AL,Lingjærde OC,Kure EH

    更新日期:2016-02-01 00:00:00

  • Expression patterns of bone morphogenetic protein antagonists in colorectal cancer desmoplastic invasion fronts.

    abstract::Bone morphogenetic proteins (BMPs) are a group of growth factors with dual functions in cancer development and progression. Recently, certain tumor-promoting roles have been identified for selected antagonists/inhibitors (BMPIs) of this developmental pathway. A recent focus on the implication of BMP in colorectal canc...

    journal_title:Molecular oncology

    pub_type: 杂志文章


    authors: Karagiannis GS,Treacy A,Messenger D,Grin A,Kirsch R,Riddell RH,Diamandis EP

    更新日期:2014-10-01 00:00:00

  • Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle.

    abstract::Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS: embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are predominant...

    journal_title:Molecular oncology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Gillis AJ,Rijlaarsdam MA,Eini R,Dorssers LC,Biermann K,Murray MJ,Nicholson JC,Coleman N,Dieckmann KP,Belge G,Bullerdiek J,Xu T,Bernard N,Looijenga LH

    更新日期:2013-12-01 00:00:00

  • Autophagy in tumour suppression and promotion.

    abstract::Autophagy, a well-described cellular mechanism for lysosomal degradation of cytoplasmic content, has emerged as a tumour suppression pathway. Recent evidence indicates that the tumour suppressor function of autophagy is mediated by scavenging of damaged oxidative organelles, thereby preventing accumulation of toxic ox...

    journal_title:Molecular oncology

    pub_type: 杂志文章,评审


    authors: Brech A,Ahlquist T,Lothe RA,Stenmark H

    更新日期:2009-08-01 00:00:00