Dissecting the signaling pathways that mediate cancer in
 PTEN
 and
 LKB1
 double-knockout mice

Chen, Jiezhong; Zhang, Xu Dong; Proud, Christopher G.

doi:10.1126/scisignal.aac8321

Cited by 17 publications

(27 citation statements)

References 17 publications

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“…Although encouraging progress in diagnosis and cancer therapy has been achieved in the past decade, the 5-year overall survival rate is less than 10% in advanced disease and chemotherapy treatment remains essential for these patients. The activation of survival signaling pathways such as EGFR, PI3K/Akt, MAPK and STAT3 plays key roles in colon cancer initiation, development, progression and drug resistance, and therapies targeting those signaling axes are beneficial 3–6. The chemotherapy drugs such as 5-fluorouracil, oxaliplatin (OXA), irinotecan, cetuximab and bevacizumab are the first-line options for treatment of metastatic colorectal cancer 7–9.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Gao

Song

Kang

et al. 2017

OTT

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Colorectal neoplasia differentially expressed (CRNDE) is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of CRNDE in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of CRNDE expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis. Overexpression of CRNDE promoted the migration and invasion potency of colorectal cancer cells. Furthermore, we found that CRNDE conferred chemoresistance in colorectal cancer cells. Knockdown of CRNDE with OXA treatment decreased cell viability and promoted DNA damage and cell apoptosis, while the overexpression of CRNDE with OXA treatment reduced DNA damage and cell apoptosis. Further in-depth mechanistic studies revealed that CRNDE functioned as a competing endogenous RNA for miR-136, led to the de-repression of its endogenous target, E2F transcription factor 1 (E2F1). Overall, our findings demonstrate that CRNDE functions as a competing endogenous RNA to promote metastasis and OXA resistance by sponging miR-136 in colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Gao

Song

Kang

et al. 2017

OTT

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“…After delivery of chemotherapeutics, liposomes can be used to interfere directly (or through the delivery of compounds that interfere with protumorigenic pathways) with, for instance, block expression of AkT and PD-L1 molecules, which have been linked with tumor progression. 61,62 Sun et al 63 showed successful siRNA and doxorubicin co-delivery to cells in vitro. With these niosomes, siRNA delivery resulted in sensitization of tumor cells for doxorubicin.…”

mentioning

confidence: 99%

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Saeed

Brakel

Zalba

et al. 2016

IJN

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Therapy of melanoma using T-cells with genetically introduced T-cell receptors (TCRs) directed against a tumor-selective cancer testis antigen (CTA) NY-ESO1 demonstrated clear antitumor responses in patients without side effects. Here, we exploited the concept of TCR-mediated targeting through introduction of single-chain variable fragment (scFv) antibodies that mimic TCRs in binding major histocompatibility complex-restricted CTA. We produced scFv antibodies directed against Melanoma AntiGEn A1 (MAGE A1) presented by human leukocyte antigen A1 (HLA-A1), in short M1/A1, and coupled these TCR-like antibodies to liposomes to achieve specific melanoma targeting. Two anti-M1/A1 antibodies with different ligand-binding affinities were derived from a phage-display library and reformatted into scFvs with an added cysteine at their carboxyl termini. Protein production conditions, ie, bacterial strain, temperature, time, and compartments, were optimized, and following production, scFv proteins were purified by immobilized metal ion affinity chromatography. Batches of pure scFvs were validated for specific binding to M1/A1-positive B-cells by flow cytometry. Coupling of scFvs to liposomes was conducted by employing different conditions, and an optimized procedure was achieved. In vitro experiments with immunoliposomes demonstrated binding of M1/A1-positive B-cells as well as M1/A1-positive melanoma cells and internalization by these cells using flow cytometry and confocal microscopy. Notably, the scFv with nonenhanced affinity of M1/A1, but not the one with enhanced affinity, was exclusively bound to and internalized by melanoma tumor cells expressing M1/A1. Taken together, antigen-mediated targeting of tumor cells as well as promoting internalization of nanoparticles by these tumor cells is mediated by TCR-like scFv and can contribute to melanoma-specific targeting.

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“…Indeed, the pro-apoptotic effects of citropten are well documented in the literature. [26][27][28][29][30][31][32] In the cited works, the antiproliferative effects of the plant molecule on tumor cells due to the alteration of specific signal transduction pathways, such as those of mitogenactivated protein kinase (MAPK) and PI3K/Akt (important in cancer survival and proliferation), suggested the use of citropten as a potential chemotherapy drug. On the other hand, the quantification of C levels per cell ( Figure 2B), which rapidly increased up to reach a sort of plateau at 48-72 hours of treatment, corroborated the finding that the plant molecules were accumulated in the cell cytoplasm but not metabolized during the time.…”

mentioning

confidence: 99%

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

Gismondi¹,

Nanni²,

Reina³

et al. 2016

IJN

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For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy

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Dissecting the signaling pathways that mediate cancer in PTEN and LKB1 double-knockout mice

Cited by 17 publications

References 17 publications

Long noncoding RNA <em>CRNDE</em> functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Long noncoding RNA <em>CRNDE</em> functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

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