Special Issue "Cancer Signaling Pathways and Crosstalk"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2011)

Special Issue Editor

Guest Editor
Dr. Don Benjamin

Growth & Development Unit, Rm. 583 Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
Fax: +41 61 267 07 59
Interests: mTOR; cancer metabolism; glycolysis; signal transduction; mRNA stability

Special Issue Information

Dear Colleagues,

Cell signaling pathways regulate cell growth, proliferation and survival. Many common genetic lesions in cancer involve signaling proteins, either as activating mutations (Ras, PI3k, Akt) or loss of function of tumor suppressors (Pten). Hyperactivation of these pathways drives tumorigenesis and supports tumor growth and leads to the establishment of pathway addiction for a particular cancer. As signals are propagated along these pathways by a relay of protein kinases, this allows access to therapeutic intervention by specific kinase inhibitors that has proven to be clinically successful. While development of kinase inhibitors continues to be actively pursued, successful treatment requires correct targeting of specific inhibitors to tumors addicted to a particular pathway. To this end, much remains to be done in identifying biomarkers for pathway addiction, and crosstalk between parallel signaling pathways in identifying patients most likely to respond to specific inhibitors.

Don Benjamin
Guest Editor

Keywords

  • cancer
  • kinase
  • phosphatase
  • signaling
  • pathway
  • receptor
  • crosstalk
  • growth
  • apoptosis

Published Papers (13 papers)

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Research

Jump to: Review

Open AccessArticle β-Catenin Is a Positive Regulator of Estrogen Receptor-α Function in Breast Cancer Cells
Cancers 2011, 3(3), 2990-3001; doi:10.3390/cancers3032990
Received: 9 June 2011 / Revised: 18 July 2011 / Accepted: 19 July 2011 / Published: 22 July 2011
Cited by 6 | PDF Full-text (1583 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human [...] Read more.
Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human breast cancer cells. Knockdown of β-catenin by RNAi resulted in significant reduction of ERα mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERα target genes pS2 and GREB1. In addition β-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. β-catenin and ERα could not be co-immunoprecipitated by ERα antibodies from lysates of E2-treated or untreated cells suggesting lack of direct physical interaction. It is concluded that β-catenin is a positive regulator of ERα mRNA and protein expression. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessArticle Microarray Analysis in a Cell Death Resistant Glioma Cell Line to Identify Signaling Pathways and Novel Genes Controlling Resistance and Malignancy
Cancers 2011, 3(3), 2827-2843; doi:10.3390/cancers3032827
Received: 27 April 2011 / Revised: 9 June 2011 / Accepted: 17 June 2011 / Published: 27 June 2011
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Abstract
Glioblastoma multiforme (GBM) is a lethal type of cancer mainly resistant to radio- and chemotherapy. Since the tumor suppressor p53 functions as a transcription factor regulating the expression of genes involved in growth inhibition, DNA repair and apoptosis, we previously assessed whether [...] Read more.
Glioblastoma multiforme (GBM) is a lethal type of cancer mainly resistant to radio- and chemotherapy. Since the tumor suppressor p53 functions as a transcription factor regulating the expression of genes involved in growth inhibition, DNA repair and apoptosis, we previously assessed whether specific differences in the modulation of gene expression are responsible for the anti-tumor properties of a dominant positive p53, chimeric tumor suppressor (CTS)-1. CTS-1 is based on the sequence of p53 and designed to resist various mechanisms of inactivation which limit the activity of p53. To identify CTS-1-regulated cell death-inducing genes, we generated a CTS-1-resistant glioma cell line (229R). We used Affymetrix whole-genome microarray expression analysis to analyze alterations in gene expression and identified a variety of CTS-1 regulated genes involved in cancer-linked processes. 313 genes were differentially expressed in Adeno-CTS-1 (Ad-CTS-1)-infected and 700 genes in uninfected 229R cells compared to matching parental cells. Ingenuity Pathway Analysis (IPA) determined a variety of differentially expressed genes in Ad-CTS-1-infected cells that were members of the intracellular networks with central tumor-involved players such as nuclear factor kappa B (NF-κB), protein kinase B (PKB/AKT) or transforming growth factor beta (TGF-β). Differentially regulated genes include secreted factors as well as intracellular proteins and transcription factors regulating not only cell death, but also processes such as tumor cell motility and immunity. This work gives an overview of the pathways differentially regulated in the resistant versus parental glioma cells and might be helpful to identify candidate genes which could serve as targets to develop novel glioma specific therapy strategies. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
Open AccessArticle Glioma Specific Extracellular Missense Mutations in the First Cysteine Rich Region of Epidermal Growth Factor Receptor (EGFR) Initiate Ligand Independent Activation
Cancers 2011, 3(2), 2032-2049; doi:10.3390/cancers3022032
Received: 25 February 2011 / Revised: 29 March 2011 / Accepted: 7 April 2011 / Published: 18 April 2011
Cited by 10 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The epidermal growth factor receptor (EGFR) is overexpressed or mutated in glioma. Recently, a series of missense mutations in the extracellular domain (ECD) of EGFR were reported in glioma patients. Some of these mutations clustered within a cysteine-rich region of the EGFR [...] Read more.
The epidermal growth factor receptor (EGFR) is overexpressed or mutated in glioma. Recently, a series of missense mutations in the extracellular domain (ECD) of EGFR were reported in glioma patients. Some of these mutations clustered within a cysteine-rich region of the EGFR targeted by the therapeutic antibody mAb806. This region is only exposed when EGFR activates and appears to locally misfold during activation. We expressed two of these mutations (R324L and E330K) in NR6 mouse fibroblasts, as they do not express any EGFR-related receptors. Both mutants were autophosphorylated in the absence of ligand and enhanced cell survival and anchorage-independent and xenograft growth. The ECD truncation that produces the de2-7EGFR (or EGFRvIII), the most common EGFR mutation in glioma, generates a free cysteine in this same region. Using a technique optimized for detecting disulfide-bonded dimers, we definitively demonstrated that the de2-7EGFR is robustly dimerized and that ablation of the free cysteine prevents dimerization and activation. Modeling of the R324L mutation suggests it may cause transient breaking of disulfide bonds, leading to similar disulfide-bonded dimers as seen for the de2-7EGFR. These ECD mutations confirm that the cysteine-rich region of EGFR around the mAb806 epitope has a significant role in receptor activation. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessArticle Ras Isoprenylation and pAkt Inhibition by Zoledronic Acid and Fluvastatin Enhances Paclitaxel Activity in T24 Bladder Cancer Cells
Cancers 2011, 3(1), 662-674; doi:10.3390/cancers3010662
Received: 29 December 2010 / Revised: 30 January 2011 / Accepted: 9 February 2011 / Published: 14 February 2011
Cited by 4 | PDF Full-text (328 KB) | HTML Full-text | XML Full-text
Abstract
Background: Bisphosphonates interfere with the mevalonate pathway and inhibit the prenylation of small GTP-binding proteins such as ras and rap. We hypothesized that zoledronic acid would synergistically inhibit T24 bladder cancer cell growth in combination with fluvastatin and paclitaxel. Methods: [...] Read more.
Background: Bisphosphonates interfere with the mevalonate pathway and inhibit the prenylation of small GTP-binding proteins such as ras and rap. We hypothesized that zoledronic acid would synergistically inhibit T24 bladder cancer cell growth in combination with fluvastatin and paclitaxel. Methods: Increasing doses of fluvastatin, zoledronic acid, and paclitaxel were investigated as single agents and in combination, and synergistic interactions were evaluated by the Chou-Talalay method. Western blots were used to assess effects on signal transduction pathways. Results: Growth of T24 was significantly inhibited with IC50 values of 2.67 ± 0.61 mM for fluvastatin and 5.35 ± 1.35 mM for zoledronic acid after 72 hours treatment. Geranylgeranyl pyrophosphate and farnesyl pyrophosphate was able to block, in part, this inhibitory activity. The combinations of zoledronic acid and paclitaxel, zoledronic acid and fluvastatin, and fluvastatin and paclitaxel were all synergistic. Both fluvastatin and zoledronic acid inhibited Ras and Rap prenylation, and the phosphorylation of ERK1/2 and AKT. The degree of inhibition of phosphorylation of these key signaling transduction pathways appears to closely correlate with their synergistic interactions. Conclusions: Zoledronic acid enhances fluvastatin and paclitaxel activity against T24 in a synergistic manner and this is mediated largely by inhibition of both the Ras/Raf/MEK/ERK and PI3K/AKT signaling pathways via isoprenylation inhibition. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Review

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Open AccessReview The Many Faces of Wnt and Pancreatic Ductal Adenocarcinoma Oncogenesis
Cancers 2011, 3(3), 3676-3686; doi:10.3390/cancers3033676
Received: 8 August 2011 / Revised: 23 August 2011 / Accepted: 15 September 2011 / Published: 21 September 2011
Cited by 2 | PDF Full-text (107 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains amongst the most lethal human cancers. PDAC is characterized by the tumor mass containing a paucity of malignant cells in association with a large desmoplastic reaction comprised of a variety of stromal components. Sporadic PDAC oncogenesis occurs [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains amongst the most lethal human cancers. PDAC is characterized by the tumor mass containing a paucity of malignant cells in association with a large desmoplastic reaction comprised of a variety of stromal components. Sporadic PDAC oncogenesis occurs as a result of the sequential acquisition of genetic aberrations occurring in core genetic pathways. Unfortunately, the average PDAC contains a large number of genetic aberrations that are not uniform between individual cancers. The interplay between the complex genetics and stromal component may represent a significant barrier to the development of effective therapy for this disease and ultimately be an important factor in PDAC lethality. The Wnt pathway has been identified as a one of the common pathways undergoing genetic alterations in PDAC. Wnt is a complex signal transduction pathway utilizing both a b-catenin dependent (canonical) and b-catenin independent (noncanonical) signals to affect a wide array of intracellular events. Wnt signal transduction is an integral component of pancreas organogenesis promoting the expansion and development of the exocrine pancreas. Pancreatic cancer may utilize the Wnt signaling pathway in concert with other signaling pathways such as notch during tumorigenesis. This review will focus on the role of Wnt signal transduction in pancreatic cancer biology. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
Open AccessReview Aberrant Signaling Pathways in Glioma
Cancers 2011, 3(3), 3242-3278; doi:10.3390/cancers3033242
Received: 12 July 2011 / Revised: 1 August 2011 / Accepted: 3 August 2011 / Published: 10 August 2011
Cited by 30 | PDF Full-text (1381 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, [...] Read more.
Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessReview Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance
Cancers 2011, 3(3), 3029-3054; doi:10.3390/cancers3033029
Received: 10 May 2011 / Revised: 6 July 2011 / Accepted: 19 July 2011 / Published: 26 July 2011
Cited by 6 | PDF Full-text (902 KB) | HTML Full-text | XML Full-text
Abstract
The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical [...] Read more.
The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
Open AccessReview Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects
Cancers 2011, 3(2), 2709-2733; doi:10.3390/cancers3022709
Received: 6 April 2011 / Revised: 2 June 2011 / Accepted: 14 June 2011 / Published: 20 June 2011
Cited by 6 | PDF Full-text (678 KB) | HTML Full-text | XML Full-text
Abstract
The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic [...] Read more.
The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1) cell cycle S-phase/G2-phase arrest; (2) prevention of cyclin inhibitor degradation; (3) protection of p53 from inactivation by phosphorylation; and (4) blockage of K+ ion channels opened by estradiol and epidermal growth factor (EGF). The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1) tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2) Herceptin antibody resistance and cardiac (arrest) arrhythmias; and (3) doxorubicin’s bystander cell toxicity. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
Open AccessReview Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives
Cancers 2011, 3(2), 2478-2500; doi:10.3390/cancers3022478
Received: 6 April 2011 / Revised: 13 May 2011 / Accepted: 16 May 2011 / Published: 24 May 2011
Cited by 12 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text
Abstract
Over the last decade, extensive studies have been made to understand the role played by the mammalian target of rapamycin (mTOR) in cancer. Knowledge in this field has been gained from discoveries in basic research as well as from observations made in [...] Read more.
Over the last decade, extensive studies have been made to understand the role played by the mammalian target of rapamycin (mTOR) in cancer. Knowledge in this field has been gained from discoveries in basic research as well as from observations made in patients treated with allosteric mTOR inhibitors such as rapamycin. Despite promising preclinical studies, targeting mTOR in cancer therapy has shown limited clinical benefits so far. However, recent findings have revealed the complexity of the functions of mTOR in cancer and have helped develop new strategies to improve the anticancer efficacy of mTOR inhibitors. In particular, a complex network between mTOR and other signaling pathways has been identified that influences the anticancer efficacy of mTOR inhibitors. In addition, an emerging role of mTOR in the tumor microenvironment has been suggested. In this review, we confront the major findings that have been made in the past, both in experimental settings as well as in clinical trials. We further review the strategies that have been designed to further improve the efficacy of therapies targeting mTOR. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessReview Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer
Cancers 2011, 3(2), 2444-2461; doi:10.3390/cancers3022444
Received: 20 April 2011 / Revised: 6 May 2011 / Accepted: 12 May 2011 / Published: 18 May 2011
Cited by 14 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different [...] Read more.
Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessReview Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways
Cancers 2011, 3(1), 1182-1194; doi:10.3390/cancers3011182
Received: 18 February 2011 / Revised: 2 March 2011 / Accepted: 3 March 2011 / Published: 8 March 2011
PDF Full-text (340 KB) | HTML Full-text | XML Full-text
Abstract
The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e., atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, [...] Read more.
The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e., atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas as well as small-cell and squamous cell lung cancer cells in cell culture. In vivo, these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers growing in athymic mice. Their signaling in cancer cells includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the MEK 1/2 kinases and 97% inhibition of the activation of basal activity of the ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. They also completely block the activity of mitogens such as epidermal growth factor’s ability to stimulate ERK and Ras. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunocytochemical studies to inhibit DNA synthesis within cancer cells. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
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Open AccessReview Muscarinic Receptor Signaling in Colon Cancer
Cancers 2011, 3(1), 971-981; doi:10.3390/cancers3010971
Received: 31 January 2011 / Revised: 14 February 2011 / Accepted: 24 February 2011 / Published: 2 March 2011
Cited by 7 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text
Abstract
According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased [...] Read more.
According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
Open AccessReview Involvement of COUP-TFs in Cancer Progression
Cancers 2011, 3(1), 700-715; doi:10.3390/cancers3010700
Received: 4 January 2011 / Revised: 25 January 2011 / Accepted: 10 February 2011 / Published: 18 February 2011
Cited by 5 | PDF Full-text (385 KB) | HTML Full-text | XML Full-text
Abstract
The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in [...] Read more.
The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis. COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression. Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial. In this review, we report both in vitro and in vivo data describing known and suspected actions of COUP-TFs that suggest that these factors are involved in modification of the phenotype of cancer cells, notably of epithelial origin. Full article
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)

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