Abstract:
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the major causes of mortality. ABT-263 is a newly synthesized, orally available Bcl-2/xL inhibitor that shows promising efficacy in HCC therapy. ABT-263 inhibits the anti-apoptotic activity of Bcl-2 and Bcl-xL, but not Mcl-1. Previous reports have shown that ABT-263 upregulates Mcl-1 in various cancer cells, which contributes to ABT-263 resistance in cancer therapy. However, the associated mechanisms are not well known. METHODS:Western blot, RNAi and CCK-8 assays were used to investigate the relationship between Mcl-1 upregulation and ABT-263 sensitivity in HCC cells. Real-time PCR and Western blot were used to detect Mcl-1 mRNA and protein levels. Luciferase reporter assay and RNA synthesis inhibition assay were adopted to analyze the mechanism of Mcl-1 mRNA upregulation. Western blot and the inhibition assays for protein synthesis and proteasome were used to explore the mechanisms of ABT-263-enhanced Mcl-1 protein stability. Trypan blue exclusion assay and flow cytometry were used to examine cell death and apoptosis. RESULTS:ABT-263 upregulated Mcl-1 mRNA and protein levels in HCC cells, which contributes to ABT-263 resistance. ABT-263 increased the mRNA level of Mcl-1 in HCC cells by enhancing the mRNA stability without influencing its transcription. Furthermore, ABT-263 increased the protein stability of Mcl-1 through promoting ERK- and JNK-induced phosphorylation of Mcl-1Thr163 and increasing the Akt-mediated inactivation of GSK-3β. Additionally, the inhibitors of ERK, JNK or Akt sensitized ABT-263-induced apoptosis in HCC cells. CONCLUSIONS:ABT-263 increases Mcl-1 stability at both mRNA and protein levels in HCC cells. Inhibition of ERK, JNK or Akt activity sensitizes ABT-263-induced apoptosis. This study may provide novel insights into the Bcl-2-targeted cancer therapeutics.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Wang B,Ni Z,Dai X,Qin L,Li X,Xu L,Lian J,He Fdoi
10.1186/1476-4598-13-98subject
Has Abstractpub_date
2014-04-30 00:00:00pages
98issn
1476-4598pii
1476-4598-13-98journal_volume
13pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract:BACKGROUND:RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-017-0683-y
更新日期:2017-07-28 00:00:00
abstract::seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, whi...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-020-01195-5
更新日期:2020-04-11 00:00:00
abstract:BACKGROUND:Human or animals lacking either JAK3 or the common gamma chain (gammac) expression display severe combined immunodeficiency disease, indicating the crucial role of JAK3 in T-cell development and the homeostasis of the immune system. JAK3 has also been suggested to contribute to the pathogenesis of tumorigene...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-36
更新日期:2010-02-11 00:00:00
abstract:BACKGROUND:New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-16
更新日期:2013-03-02 00:00:00
abstract:BACKGROUND:Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but t...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0641-8
更新日期:2017-03-29 00:00:00
abstract:BACKGROUND:Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confir...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0787-z
更新日期:2018-02-19 00:00:00
abstract:BACKGROUND:Aberrant expression of microRNAs in different human cancer types has been widely reported. MiR-218 acts as a tumor suppressor in diverse human cancer types impacting regulation of multiple genes in oncogenic pathways. Here, we evaluated the expression and function of miR-218 in human lung cancer and ALDH pos...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0710-z
更新日期:2017-08-22 00:00:00
abstract:BACKGROUND:Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-131
更新日期:2014-05-29 00:00:00
abstract:BACKGROUND:Granulosa cell tumors (GCTs) are relatively rare and are subtypes of the sex-cord stromal neoplasms. Methylation induced silencing in the promoters of genes such as tumor suppressor genes, DNA repair genes and pro-apoptotic genes is recognised as a critical factor in cancer development. METHODS:We examined ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-3-33
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Non-small cell lung cancer (NSCLC) is the number one cancer killer. Tumor-initiating cells (TICs) are responsible for tumor progression and recurrence. Emerging evidences suggest that small nucleolar RNAs (snoRNAs) play malfunctioning roles in lung tumorigenesis. This study aims to determine if snoRNAs have ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-104
更新日期:2014-05-06 00:00:00
abstract:BACKGROUND:Gastrointestinal stromal tumour (GIST) is the most common soft tissue sarcoma. The identification of the molecular mechanisms regulating GIST progression is vital for its treatment and prevention. Increasing reports have demonstrated that epigenetic alterations play critical roles in GIST development. Howeve...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0861-6
更新日期:2018-07-30 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses among all cancers. Over the past several decades, investigators have made great advances in the research of PDAC pathogenesis. Importantly, identification of pancreatic cancer stem cells (PCSCs) in pancreatic cancer cases has increased our unders...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-12-159
更新日期:2013-12-10 00:00:00
abstract:BACKGROUND:The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in v...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-109
更新日期:2013-09-24 00:00:00
abstract:BACKGROUND:Tumor cells produce various cytokines and chemokines that attract leukocytes. Leukocytes can amplify parenchymal innate immune responses, and have been shown to contribute to tumor promotion. Neutrophils are among the first cells to arrive at sites of inflammation, and the increased number of tumor-associate...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-154
更新日期:2013-12-09 00:00:00
abstract::Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects t...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0913-y
更新日期:2018-11-26 00:00:00
abstract:BACKGROUND:Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC arising from mutations in the von Hippel Lindau (VHL) tumor suppressor. Successful RCC tumor suppression by VHL requires the negative regulation of hypoxia inducible factor alpha (HIF alpha) protein a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-5-66
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol con...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-0949-7
更新日期:2019-02-08 00:00:00
abstract:BACKGROUND:Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safet...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-47
更新日期:2009-07-14 00:00:00
abstract:BACKGROUND:The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFbeta is a transcriptional co-activator that is ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-171
更新日期:2010-06-30 00:00:00
abstract:BACKGROUND:High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; however, its' clinical significance and origin are unclear. We evaluated the diagnostic and prognostic value, and origin of whole blood NEAT1 in colorectal...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0455-5
更新日期:2015-11-09 00:00:00
abstract:BACKGROUND:Estrogen receptor-positive (ER+) breast cancers represent approximately two-thirds of all breast cancers and have a sustained risk of late disease recurrence. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown significant efficacy in ER+ breast cancer. However, their effects are still limited by ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-020-01210-9
更新日期:2020-05-11 00:00:00
abstract:BACKGROUND:Since tumor growth requires reactivation of telomerase (hTERT), this enzyme is a challenging target for drug development. Therefore, it is of great interest to identify telomerase expression and activity regulators. Retinoids are well-known inducers of granulocytic maturation associated with hTERT repression...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0835-8
更新日期:2018-04-27 00:00:00
abstract:BACKGROUND:In the current study we investigated the role of caveolin-1 (cav-1) in pancreatic adenocarcinoma (PC) cell migration and invasion; initial steps in metastasis. Cav-1 is the major structural protein in caveolae; small Omega-shaped invaginations within the plasma membrane. Caveolae are involved in signal trans...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-4-21
更新日期:2005-06-21 00:00:00
abstract::Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-019-1057-4
更新日期:2019-08-20 00:00:00
abstract:BACKGROUND:Interferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown. METHODS:Differentially expressed lncRNAs were screened under IFNα stimulation using lnc...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-1123-y
更新日期:2020-01-06 00:00:00
abstract:BACKGROUND:Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0588-9
更新日期:2017-02-16 00:00:00
abstract:BACKGROUND:In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, inc...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-3-31
更新日期:2004-11-17 00:00:00
abstract:BACKGROUND:Epigenetic control is essential for maintenance of tissue hierarchy and correct differentiation. In cancer, this hierarchical structure is altered and epigenetic control deregulated, but the relationship between these two phenomena is still unclear. CD133 is a marker for adult stem cells in various tissues a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-94
更新日期:2011-07-29 00:00:00
abstract:BACKGROUND:A maximum entropy approach is proposed to predict the cytotoxic effects of a panel of colchicine derivatives in several human cancer cell lines. Data was obtained from cytotoxicity assays performed with 21 drug molecules from the same family of colchicine compounds and correlate these results with independen...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-131
更新日期:2010-05-30 00:00:00
abstract:BACKGROUND:Tumor spreading is the major threat for cancer patients. The recently published anti-cancer drug salinomycin raised hope for an improved treatment by targeting therapy-refractory cancer stem cells. However, an unambiguous role of salinomycin against cancer cell migration and metastasis formation remains elus...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-16
更新日期:2014-01-27 00:00:00