Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.

Abstract:

:The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes, mTORC1 and mTORC2 plays an important role in tumor growth. Whereas the role of mTORC1 has been well characterized in this process, little is known about the functions of mTORC2 in cancer progression. In this study, we explored the specific role of mTORC2 in colon cancer using a short hairpin RNA expression system to silence the mTORC2-associated protein rictor. We found that downregulation of rictor in HT29 and LS174T colon cancer cells significantly reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice xenograft model. Taken together, these results show that the inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting mTORC2 may provide a novel treatment strategy for colorectal cancer.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Roulin D,Cerantola Y,Dormond-Meuwly A,Demartines N,Dormond O

doi

10.1186/1476-4598-9-57

subject

Has Abstract

pub_date

2010-03-12 00:00:00

pages

57

issn

1476-4598

pii

1476-4598-9-57

journal_volume

9

pub_type

杂志文章
  • Dovitinib synergizes with oxaliplatin in suppressing cell proliferation and inducing apoptosis in colorectal cancer cells regardless of RAS-RAF mutation status.

    abstract:BACKGROUND:Cancer is the result of a multistep process of genomic alterations, including mutations in key regulatory proteins that result in loss of balanced gene expression and subsequent malignant transformation. Throughout the various stages of colorectal carcinoma (CRC), complex genetic alterations occur, of which ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-13-21

    authors: Gaur S,Chen L,Ann V,Lin WC,Wang Y,Chang VH,Hsu NY,Shia HS,Yen Y

    更新日期:2014-02-04 00:00:00

  • Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.

    abstract:BACKGROUND:Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-016-0575-6

    authors: Niu Y,Ma F,Huang W,Fang S,Li M,Wei T,Guo L

    更新日期:2017-01-09 00:00:00

  • MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma.

    abstract:BACKGROUND:Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify different...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-124

    authors: Zhang Z,Tang H,Wang Z,Zhang B,Liu W,Lu H,Xiao L,Liu X,Wang R,Li X,Wu M,Li G

    更新日期:2011-09-30 00:00:00

  • The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth.

    abstract:BACKGROUND:Human clear cell renal cell carcinoma (CRCC) remains resistant to therapies. Recent advances in Hypoxia Inducible Factors (HIF) molecular network led to targeted therapies, but unfortunately with only limited clinical significance. Elucidating the molecular processes involved in kidney tumorigenesis and resi...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-8-123

    authors: Dormoy V,Danilin S,Lindner V,Thomas L,Rothhut S,Coquard C,Helwig JJ,Jacqmin D,Lang H,Massfelder T

    更新日期:2009-12-16 00:00:00

  • Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling.

    abstract:BACKGROUND:Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been rep...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-12-41

    authors: Lang M,Borgmann M,Oberhuber G,Evstatiev R,Jimenez K,Dammann KW,Jambrich M,Khare V,Campregher C,Ristl R,Gasche C

    更新日期:2013-05-13 00:00:00

  • Perforin-dependent direct cytotoxicity in natural killer cells induces considerable knockdown of spontaneous lung metastases and computer modelling-proven tumor cell dormancy in a HT29 human colon cancer xenograft mouse model.

    abstract:BACKGROUND:For long, natural killer (NK) cells have been suspected to play a critical role in suppressing the development of spontaneous metastases in cancer patients. Despite a wide range of studies it remains unclear so far to what extent primary tumor growth together with formation of distant metastases and NK cell ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-13-244

    authors: Brodbeck T,Nehmann N,Bethge A,Wedemann G,Schumacher U

    更新日期:2014-11-05 00:00:00

  • Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27.

    abstract:BACKGROUND:Hypoxia can halt cell cycle progression of several cell types at the G1/S interface. The arrest needs to be overcome by cancer cells. We have previously shown that the hypoxia-inducible cellular oxygen sensor PHD3/EGLN3 enhances hypoxic cell cycle entry at the G1/S boundary. METHODS:We used PHD3 knockdown b...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-015-0410-5

    authors: Högel H,Miikkulainen P,Bino L,Jaakkola PM

    更新日期:2015-07-30 00:00:00

  • circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway.

    abstract:BACKGROUND:Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. METHODS:Th...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-020-01279-2

    authors: Gao W,Guo H,Niu M,Zheng X,Zhang Y,Xue X,Bo Y,Guan X,Li Z,Guo Y,He L,Zhang Y,Li L,Cao J,Wu Y

    更新日期:2020-11-24 00:00:00

  • CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.

    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

    authors: Pasquier J,Gosset M,Geyl C,Hoarau-Véchot J,Chevrot A,Pocard M,Mirshahi M,Lis R,Rafii A,Touboul C

    更新日期:2018-02-19 00:00:00

  • PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.

    abstract:BACKGROUND:Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and p...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-019-0940-3

    authors: Tan L,Mai D,Zhang B,Jiang X,Zhang J,Bai R,Ye Y,Li M,Pan L,Su J,Zheng Y,Liu Z,Zuo Z,Zhao Q,Li X,Huang X,Yang J,Tan W,Zheng J,Lin D

    更新日期:2019-01-12 00:00:00

  • ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex.

    abstract:BACKGROUND:Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear. METHODS AND RESULTS:The ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-13-181

    authors: Zhang Q,Yang Z,Jia Z,Liu C,Guo C,Lu H,Chen P,Ma K,Wang W,Zhou C

    更新日期:2014-07-29 00:00:00

  • Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy.

    abstract:BACKGROUND:Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy affecting children. Despite significant progress and success in the treatment of ALL, a significant number of children continue to relapse and for them, outcome remains poor. Therefore, the search for novel therapeutic approaches ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-6-46

    authors: Sengupta TK,Leclerc GM,Hsieh-Kinser TT,Leclerc GJ,Singh I,Barredo JC

    更新日期:2007-07-10 00:00:00

  • Cripto-1 acts as a functional marker of cancer stem-like cells and predicts prognosis of the patients in esophageal squamous cell carcinoma.

    abstract:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is highly malignant with highly invasive and metastatic capabilities and poor prognosis. It is believed that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity, invasion and metastasis of ESCC. However, the properties of ECSLCs vary with differe...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-017-0650-7

    authors: Liu Q,Cui X,Yu X,Bian BS,Qian F,Hu XG,Ji CD,Yang L,Ren Y,Cui W,Zhang X,Zhang P,Wang JM,Cui YH,Bian XW

    更新日期:2017-04-21 00:00:00

  • Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression.

    abstract:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and local...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-018-0930-x

    authors: Chen Y,Wang D,Peng H,Chen X,Han X,Yu J,Wang W,Liang L,Liu Z,Zheng Y,Hu J,Yang L,Li J,Zhou H,Cui X,Li F

    更新日期:2019-01-04 00:00:00

  • CircRNA inhibits DNA damage repair by interacting with host gene.

    abstract:BACKGROUND:Deregulated circular RNAs (circRNAs) are associated with the development of cancer and therapy resistance. However, functional research of circRNAs mostly focus on potential miRNA or protein binding and more potential regulation of circRNA on host gene DNA in cancers are yet to be inspected. METHOD:We perfo...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-020-01246-x

    authors: Xu X,Zhang J,Tian Y,Gao Y,Dong X,Chen W,Yuan X,Yin W,Xu J,Chen K,He C,Wei L

    更新日期:2020-08-24 00:00:00

  • Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer.

    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

    authors: Zinn RL,Gardner EE,Dobromilskaya I,Murphy S,Marchionni L,Hann CL,Rudin CM

    更新日期:2013-03-02 00:00:00

  • Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile.

    abstract:BACKGROUND:In high grade gliomas, 1p19q codeletion and EGFR amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with EGFR amplification, identified by CGH-array. RESULTS:The two...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-7-41

    authors: Ducray F,Idbaih A,de Reyniès A,Bièche I,Thillet J,Mokhtari K,Lair S,Marie Y,Paris S,Vidaud M,Hoang-Xuan K,Delattre O,Delattre JY,Sanson M

    更新日期:2008-05-20 00:00:00

  • Pregnane X receptor is associated with unfavorable survival and induces chemotherapeutic resistance by transcriptional activating multidrug resistance-related protein 3 in colorectal cancer.

    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

    authors: Dong Y,Wang Z,Xie GF,Li C,Zuo WW,Meng G,Xu CP,Li JJ

    更新日期:2017-03-29 00:00:00

  • Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity.

    abstract:BACKGROUND:Changes in glycogen metabolism is an essential feature among the various metabolic adaptations used by cancer cells to adjust to the conditions imposed by the tumor microenvironment. Our previous study showed that glycogen branching enzyme (GBE1) is downstream of the HIF1 pathway in hypoxia-conditioned lung ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-019-1027-x

    authors: Li L,Yang L,Cheng S,Fan Z,Shen Z,Xue W,Zheng Y,Li F,Wang D,Zhang K,Lian J,Wang D,Zhu Z,Zhao J,Zhang Y

    更新日期:2019-06-20 00:00:00

  • Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies.

    abstract::Cancer is a leading cause of death worldwide, particularly because of its high mortality rate in patients who are diagnosed at late stages. Conventional biomarkers originating from blood are widely used for cancer diagnosis, but their low sensitivity and specificity limit their widespread application in cancer screeni...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-020-01298-z

    authors: Wang S,Zhang K,Tan S,Xin J,Yuan Q,Xu H,Xu X,Liang Q,Christiani DC,Wang M,Liu L,Du M

    更新日期:2021-01-11 00:00:00

  • Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a poor prognosis worldwide. While early stage tumours can be treated with curative approaches such as liver transplantation or surgical resection, these are only suitable for a minority of patients. Those with advanced stage disease are on...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-017-0734-4

    authors: Huo X,Han S,Wu G,Latchoumanin O,Zhou G,Hebbard L,George J,Qiao L

    更新日期:2017-10-23 00:00:00

  • A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12.

    abstract::Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the ...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/1476-4598-9-242

    authors: Klinke DJ 2nd

    更新日期:2010-09-15 00:00:00

  • The relevance of tyrosine kinase inhibitors for global metabolic pathways in cancer.

    abstract::Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyro...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-018-0798-9

    authors: Poliaková M,Aebersold DM,Zimmer Y,Medová M

    更新日期:2018-02-19 00:00:00

  • Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers.

    abstract:BACKGROUND:Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA dama...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-8-43

    authors: Cheung CH,Chen HH,Kuo CC,Chang CY,Coumar MS,Hsieh HP,Chang JY

    更新日期:2009-07-03 00:00:00

  • mRNA-to-protein translation in hypoxia.

    abstract::Cells respond to hypoxia by shifting cellular processes from general housekeeping functions to activating specialized hypoxia-response pathways. Oxygen plays an important role in generating ATP to maintain a productive rate of protein synthesis in normoxia. In hypoxia, the rate of the canonical protein synthesis pathw...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-019-0968-4

    authors: Chee NT,Lohse I,Brothers SP

    更新日期:2019-03-30 00:00:00

  • Antisense gapmers selectively suppress individual oncogenic p73 splice isoforms and inhibit tumor growth in vivo.

    abstract:BACKGROUND:Differential mRNA splicing and alternative promoter usage of the TP73 gene results in the expression of multiple NH2-truncated isoforms that act as oncogenes. Abundant levels of these p73 variants in a variety of human cancers correlated with adverse clinical prognosis and response failure to conventional th...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-8-61

    authors: Emmrich S,Wang W,John K,Li W,Pützer BM

    更新日期:2009-08-11 00:00:00

  • miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer.

    abstract:INTRODUCTION:ERBB3, one of the four members of the ErbB family of receptor tyrosine kinases, plays an important role in breast cancer etiology and progression. In the present study, we aimed to identify novel miRNAs that can potentially target ERBB3 and their biological functions. METHOD:The expression levels of miR-1...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-13-220

    authors: Yan X,Chen X,Liang H,Deng T,Chen W,Zhang S,Liu M,Gao X,Liu Y,Zhao C,Wang X,Wang N,Li J,Liu R,Zen K,Zhang CY,Liu B,Ba Y

    更新日期:2014-09-24 00:00:00

  • Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity.

    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

    authors: Yu S,Yi M,Qin S,Wu K

    更新日期:2019-08-20 00:00:00

  • Regulation of β-catenin by t-DARPP in upper gastrointestinal cancer cells.

    abstract:BACKGROUND:Truncated dopamine and cyclic-AMP-regulated phosphoprotein (t-DARPP) is frequently overexpressed in gastrointestinal malignancies. In this study, we examined the role of t-DARPP in regulating β-catenin. RESULTS:The pTopFlash construct that contains multiple TCF/LEF-binding sites was used as a measure of β-c...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-32

    authors: Vangamudi B,Zhu S,Soutto M,Belkhiri A,El-Rifai W

    更新日期:2011-03-29 00:00:00

  • The MUC gene family: their role in diagnosis and early detection of pancreatic cancer.

    abstract::The early diagnosis of pancreatic cancer, as well as distinguishing between chronic pancreatitis and malignant pancreatic disease, remains still a clinical problem. Presently, there is no specific tumor marker for diagnosing pancreatic cancer. Mucin-associated marker like CA 19-9 are the most widely available pancreat...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:

    authors: Ringel J,Löhr M

    更新日期:2003-01-07 00:00:00