HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer.


:Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission on chemoresistance in colorectal cancer is unclear. Here, we found that the release of high-mobility group box 1 protein (HMGB1) in conditioned medium from dying cells by chemotherapeutic drugs and resistant cells, which triggered Drp1 phosphorylation via its receptor for advanced glycation end product (RAGE). RAGE signals ERK1/2 activation to phosphorylate Drp1 at residue S616 triggerring autophagy for chemoresistance and regrowth in the surviving cancer cells. Abolishment of Drp1 phosphorylation by HMGB1 inhibitor and RAGE blocker significantly enhance sensitivity to the chemotherapeutic treatment by suppressing autophagy. Furthermore, patients with high phospho-Drp1Ser616 are associated with high risk on developing tumor relapse, poor 5-year disease-free survival (DFS) and 5-year overall survival (OS) after neoadjuvant chemoradiotherapy (neoCRT) treatment in locally advanced rectal cancer (LARC). Moreover, patients with RAGE-G82S polymorphism (rs2070600) are associated with high phospho-Drp1Ser616 within tumor microenvironment. These findings suggest that the release of HMGB1 from dying cancer cells enhances chemoresistance and regrowth via RAGE-mediated ERK/Drp1 phosphorylation.


Cell Death Dis


Cell death & disease


Huang CY,Chiang SF,Chen WT,Ke TW,Chen TW,You YS,Lin CY,Chao KSC,Huang CY




Has Abstract


2018-09-26 00:00:00












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    abstract::Despite successful antiretroviral drug therapy, a subset of human immunodeficiency virus-1 (HIV)-positive individuals still display synaptodendritic simplifications and functional cognitive impairments referred to as HIV-associated neurocognitive disorders (HANDs). The neurological damage observed in HAND subjects can...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wenzel ED,Speidell A,Flowers SA,Wu C,Avdoshina V,Mocchetti I

    更新日期:2019-09-12 00:00:00

  • Gefitinib targets ZAP-70-expressing chronic lymphocytic leukemia cells and inhibits B-cell receptor signaling.

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Dielschneider RF,Xiao W,Yoon JY,Noh E,Banerji V,Li H,Marshall AJ,Johnston JB,Gibson SB

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  • miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling.

    abstract::Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes l...

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    authors: Huang X,Xiao S,Zhu X,Yu Y,Cao M,Zhang X,Li S,Zhu W,Wu F,Zheng X,Jin L,Xie C,Huang X,Zou P,Li X,Cui R

    更新日期:2020-09-22 00:00:00

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    journal_title:Cell death & disease

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    authors: Scheiman J,Jamieson KV,Ziello J,Tseng JC,Meruelo D

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  • Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia.

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    journal_title:Cell death & disease

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    authors: Berrazouane S,Boisvert M,Salti S,Mourad W,Al-Daccak R,Barabé F,Aoudjit F

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  • E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway.

    abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yu Y,Zhao D,Li K,Cai Y,Xu P,Li R,Li J,Chen X,Chen P,Cui G

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    abstract::Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcription factor Isl1 t...

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    authors: Su T,Liu H,Zhang D,Xu G,Liu J,Evans SM,Pan J,Cui S

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    journal_title:Cell death & disease

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    authors: Yu F,Zhang W,Yan C,Yan D,Zhou M,Chen J,Zhao X,Zhu A,Zhou J,Liu H,Sun H,Fu Y

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    journal_title:Cell death & disease

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    authors: Cheteh EH,Augsten M,Rundqvist H,Bianchi J,Sarne V,Egevad L,Bykov VJ,Östman A,Wiman KG

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    authors: Ousingsawat J,Wanitchakool P,Schreiber R,Kunzelmann K

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    journal_title:Cell death & disease

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  • Novel osmotin attenuates glutamate-induced synaptic dysfunction and neurodegeneration via the JNK/PI3K/Akt pathway in postnatal rat brain.

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    journal_title:Cell death & disease

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    authors: Shah SA,Lee HY,Bressan RA,Yun DJ,Kim MO

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    journal_title:Cell death & disease

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    authors: Trayssac M,Clarke CJ,Stith JL,Snider JM,Newen N,Gault CR,Hannun YA,Obeid LM

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    journal_title:Cell death & disease

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    authors: Lee SJ,Lee HJ,Jung YH,Kim JS,Choi SH,Han HJ

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    journal_title:Cell death & disease

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    authors: Zhu S,Zhang J,Xu F,Xu E,Ruan W,Ma Y,Huang Q,Lai M

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  • Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

    abstract::A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell...

    journal_title:Cell death & disease

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    authors: Angioni R,Sánchez-Rodríguez R,Munari F,Bertoldi N,Arcidiacono D,Cavinato S,Marturano D,Zaramella A,Realdon S,Cattelan A,Viola A,Molon B

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  • P53-induced miR-1249 inhibits tumor growth, metastasis, and angiogenesis by targeting VEGFA and HMGA2.

    abstract::MicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our st...

    journal_title:Cell death & disease

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    authors: Chen X,Zeng K,Xu M,Liu X,Hu X,Xu T,He B,Pan Y,Sun H,Wang S

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  • Increased survival and cell cycle progression pathways are required for EWS/FLI1-induced malignant transformation.

    abstract::Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mes...

    journal_title:Cell death & disease

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    authors: Javaheri T,Kazemi Z,Pencik J,Pham HT,Kauer M,Noorizadeh R,Sax B,Nivarthi H,Schlederer M,Maurer B,Hofbauer M,Aryee DN,Wiedner M,Tomazou EM,Logan M,Hartmann C,Tuckermann JP,Kenner L,Mikula M,Dolznig H,Üren A,Richt

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  • CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling.

    abstract::Prostate cancer stem cells (PCSCs) play a critical role in prostate cancer progression and metastasis, which remains an obstacle for successful prostate cancer treatment. Tumor-associated macrophages (TAMs) are the most abundant immune cell population within the tumor microenvironment (TME). Systematic investigation o...

    journal_title:Cell death & disease

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    authors: Huang R,Wang S,Wang N,Zheng Y,Zhou J,Yang B,Wang X,Zhang J,Guo L,Wang S,Chen Z,Wang Z,Xiang S

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  • Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism.

    abstract::Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or ...

    journal_title:Cell death & disease

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    authors: Chen H,Zhang H,Zheng Y,Min X,Luo Y,Zhou W,Ma F,Li J,Lu Q,Zhang C,Cai H,Sha W

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  • EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury.

    abstract::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Tsenkina Y,Ricard J,Runko E,Quiala-Acosta MM,Mier J,Liebl DJ

    更新日期:2015-10-15 00:00:00

  • Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma.

    abstract::Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated...

    journal_title:Cell death & disease

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    authors: Liu R,Wang X,Curtiss C,Landas S,Rong R,Sheikh MS,Huang Y

    更新日期:2018-01-18 00:00:00

  • Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis.

    abstract::Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main cell type of extracellular matrix (ECM) deposition during hepatic fibrosis. Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been reported, but the functional roles and mechanisms of DNA methylation in hepatic fib...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Chen X,Li WX,Chen Y,Li XF,Li HD,Huang HM,Bu FT,Pan XY,Yang Y,Huang C,Meng XM,Li J

    更新日期:2018-10-03 00:00:00

  • Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC.

    abstract::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...

    journal_title:Cell death & disease

    pub_type: 杂志文章


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

    更新日期:2020-08-18 00:00:00

  • Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression.

    abstract::Estrogen receptor-alpha positive (ER(+)) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER(+) mammary luminal tumors arising in Tip30(-/-)MMTV-Neu mice exhibited increased enrichment of lumina...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Chen F,Li A,Gao S,Hollern D,Williams M,Liu F,VanSickle EA,Andrechek E,Zhang C,Yang C,Luo R,Xiao H

    更新日期:2014-05-22 00:00:00

  • MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro.

    abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yadav SK,Kambis TN,Kar S,Park SY,Mishra PK

    更新日期:2020-03-13 00:00:00

  • Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury.

    abstract::Phosphatase and tensin homolog (PTEN) regulates apoptosis and axonal growth in the developing and adult central nervous system (CNS). Here, we show that human PTEN C-terminal PDZ interactions play a critical role in neuronal apoptosis and axon regeneration after traumatic CNS injury and stroke, highlighted by the find...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Shabanzadeh AP,D'Onofrio PM,Magharious M,Choi KAB,Monnier PP,Koeberle PD

    更新日期:2019-07-29 00:00:00

  • Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death.

    abstract::The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' com...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Kondratskyi A,Yassine M,Slomianny C,Kondratska K,Gordienko D,Dewailly E,Lehen'kyi V,Skryma R,Prevarskaya N

    更新日期:2014-04-24 00:00:00

  • Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

    abstract::High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated...

    journal_title:Cell death & disease

    pub_type: 杂志文章,收录出版


    authors: Peng Y,Yang C,Shi X,Li L,Dong H,Liu C,Fang Z,Wang Z,Ming S,Liu M,Xie B,Gao X,Sun Y

    更新日期:2019-01-15 00:00:00