Abstract:
:The colorectal cancer is the leading contributor of cancer-related mortality. Mammalian target of rapamycin (mTOR), existing in 2 complexes (mTORC1/2), is frequently dysregulated and constitutively activated in colorectal cancers. It represents an important drug target. Here we found that INK-128, the novel ATP-competitive kinase inhibitor of mTOR, blocked both mTORC1 and mTORC2 activation in colorectal cancer cells (both primary and transformed cells). The immunoprecipitation results showed that the assembly of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-Sin1 association) was also disrupted by INK-128. INK-128 inhibited colorectal cancer cell growth and survival, and induced both apoptotic and non-apoptotic cancer cell death. Further, INK-128 showed no effect on Erk/MAPK activation, while MEK/Erk inhibition by MEK-162 enhanced INK-128-induced cytotoxicity in colorectal cancer cells. Meanwhile, INK-128 downregulated Fascin1 (FSCN1)/E-Cadherin expressions and inhibited HT-29 cell in vitro migration. In vivo, daily INK-128 oral administration inhibited HT-29 xenograft growth in mice, which was further enhanced by MEK-162 administration. Finally, we found that INK-128 sensitized 5-fluorouracil-(5-FU)-mediated anti-HT-29 activity in vivo and in vitro. Thus, our preclinical studies strongly suggest that INK-128 might be investigated for colorectal cancer treatment in clinical trials.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Li C,Cui JF,Chen MB,Liu CY,Liu F,Zhang QD,Zou J,Lu PHdoi
10.4161/15384047.2014.972274subject
Has Abstractpub_date
2015-01-01 00:00:00pages
34-42issue
1eissn
1538-4047issn
1555-8576journal_volume
16pub_type
杂志文章abstract:BACKGROUND:Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1803009
更新日期:2020-09-01 00:00:00
abstract::Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological res...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26106
更新日期:2013-11-01 00:00:00
abstract::To investigate the diagnostic potential of DNA methylation-based markers in tissue samples of DCIS, we examined the prevalence and extent of methylation in breast ductal carcinoma in situ (DCIS) samples from North American and Korean women. Quantitative multiplex-methylation specific PCR (QM-MSP) of ten genes was perf...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.9.6425
更新日期:2008-09-01 00:00:00
abstract::MDM2 antagonists stabilize and activate wild-type p53, and histone methyltransferase (HMT) inhibitors reduce methylation on histone lysines and arginines. Both MDM2 antagonists and HMT inhibitors are being developed as cancer therapeutics. Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1433500
更新日期:2018-06-03 00:00:00
abstract::Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.4.2512
更新日期:2006-04-01 00:00:00
abstract::Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3702
更新日期:2007-03-01 00:00:00
abstract::Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody (mAb) registered for treating head and neck tumours. The present study was designed to evaluate the systemic and skin toxicity of chronic intravenous administration of the h-R3 in a relevant species demonstrated by comparing th...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.9.4539
更新日期:2007-09-01 00:00:00
abstract::The 26S proteasome is a large multi-subunit protein complex found in the cytoplasm and nucleus of mammalian cells which plays a critical role in intracellular proteolysis. It has been found that the 26S proteasome degrades multiple important substrates which are associated with tumor growth and development. Emerging e...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.7.2971
更新日期:2006-07-01 00:00:00
abstract::Circulating tumor cells (CTC) enter the blood from many carcinomas and represent a likely source of metastatic dissemination. In contrast to the peripheral circulation, KRAS mutation- positive CTC thrive in the portal venous blood of patients with pancreatic ductal adenocarcinoma (PDAC). To analyze the essential inter...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1480292
更新日期:2018-01-01 00:00:00
abstract::The mitochondrial production of reactive oxygen species has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitoc...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.11.3302
更新日期:2006-11-01 00:00:00
abstract::Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1450113
更新日期:2018-08-03 00:00:00
abstract::Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative ef...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.6.12532
更新日期:2010-09-15 00:00:00
abstract::Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1078022
更新日期:2015-01-01 00:00:00
abstract::MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4486
更新日期:2007-08-01 00:00:00
abstract::The antiproliferative effects and apoptosis inducing abilities of four 18beta-glycyrrhetinic acid (GA) derivatives, methyl 2-cyano-3,11-dioxooleana-1,12-dien-30-oate (CDODO-Me-11), methyl 2-cyano-3,12-dioxooleana-1,12-dien-30-oate (CDODO-Me-12) and their non-esters were investigated in human leukemia cells. Methyl est...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.2.10287
更新日期:2010-01-01 00:00:00
abstract::Methylthioadenosine phosphorylase (MTAP), a key enzyme in the catabolism of 5'-deoxy-5'-methylthioadenosine (MTA), catalyzes the formation of adenine and 5-methylthioribose-1-phosphate. MTAP is expressed in all cells throughout the body, but a significant percentage of human tumors have lost MTAP expression, thereby m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21115
更新日期:2012-09-01 00:00:00
abstract::Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in gastric cancer has not been fully understood. In this study, we reported that miR-101 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.987523
更新日期:2015-01-01 00:00:00
abstract::Acquired mutations in anaplastic lymphoma kinase (ALK) gene have been implicated as the major resistance mechanism to ALK inhibitors; however, information on the treatment options after acquiring novel ALK secondary mutations is limited. Herein, we report the efficacy of lorlatinib upon the detection of a novel ALK G1...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1836947
更新日期:2021-01-02 00:00:00
abstract::TPCK is widely used as an inhibitor of chymotrypsin-like proteases but has recently been identified as an inhibitor of the PDK1/Akt pathway. In this study, we show that TPCK inhibits TRAIL-induced caspase activity but potentiates wortmannin-dependent caspase activity in prostatic carcinoma cell lines. The inhibitory a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.8.970
更新日期:2004-08-01 00:00:00
abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1345393
更新日期:2017-12-02 00:00:00
abstract::The objective of the present study was to evaluate CA19-9 and CK8/18 expression patterns in pancreatic cancer cell lines induced by 5-fluorouracil (5-Fu), and in circulating tumor cells (CTCs) in peripheral blood of patients previously untreated with advanced pancreatic cancer. Furthermore, the goal was to test the re...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.8.15960
更新日期:2011-10-15 00:00:00
abstract::Prior to 2011, only 2 systemic treatments were approved for the treatment of melanoma and these had limited efficacy. In the past 4 years, 6 novel agents have received FDA approval. Herein, we will focus on 4 recently published NEJM papers reporting the results of clinical trials, comprising 4 agents targeting the MAP...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1046650
更新日期:2015-01-01 00:00:00
abstract::Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor s...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1026512
更新日期:2015-01-01 00:00:00
abstract::Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972183
更新日期:2014-01-01 00:00:00
abstract::WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are t...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.9.3151
更新日期:2006-09-01 00:00:00
abstract::Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Soci...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.9.17677
更新日期:2011-11-01 00:00:00
abstract::Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6966
更新日期:2008-12-01 00:00:00
abstract::Prostate-Specific Membrane Antigen (PSMA) is a glutamate carboxypeptidase II that is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types but is not expressed by endothelial cells in normal tissue. PSMA possesses the hydrolytic properties of an N-acetyla...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.6.846
更新日期:2004-06-01 00:00:00
abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.785
更新日期:2004-03-01 00:00:00
abstract::The impact of environmental mutagens and carcinogens on the mammary gland has recently received a lot of attention. Among the most generally accepted carcinogenic agents identified as factors that may increase breast cancer incidence are ionizing radiation and elevated estrogen levels. However, the molecular mechanism...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.24599
更新日期:2013-07-01 00:00:00