共查询到20条相似文献,搜索用时 46 毫秒
1.
The Hedgehog family of growth factors activate a highly conserved signaling system for cell-cell communication that regulates
cell proliferation and differentiation during development. Abnormal activation of the Hedgehog pathway has been demonstrated
in a variety of human tumors, including those of the skin, brain, lung and digestive tract. Hedgehog pathway activity in these
tumors is required for cancer cell proliferation and tumor growth. Recent studies have uncovered the role for Hedgehog signaling
in advanced prostate cancer and demonstrated that autocrine signaling by tumor cells is required for proliferation, viability,
and invasive behavior. The level of Hedgehog activity correlates with the severity of the tumor and is both necessary and
sufficient for metastatic behavior. Blockade of Hedgehog signaling leads to tumor shrinkage and remission in preclinical tumor
xenograft models. Thus, Hedgehog signaling represents a novel pathway in prostate cancer that offers opportunities for prognostic
biomarker development, drug targeting and therapeutic response monitoring.
Received 18 August 2005; received after revision 30 September 2005; accepted 1 November 2005 相似文献
2.
Xiangqian Zhang Ye Tian Yanling Yang Jijun Hao 《Cellular and molecular life sciences : CMLS》2017,74(15):2773-2782
Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment. Here, we review the therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment. 相似文献
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Hedgehog signaling in pancreas development and disease 总被引:6,自引:0,他引:6
Since its discovery, numerous studies have shown that the Hedgehog (Hh) signaling pathway plays an instrumental role during
diverse processes of cell differentiation and organ development. More recently, it has become evident that Hh signaling is
not restricted to developmental events, but retains some of its activity during adult life. In mature tissues, Hh signaling
has been implicated in the maintenance of stem cell niches in the brain, renewal of the gut epithelium and differentiation
of hematopoietic cells. In addition to the basal function in adult tissue, deregulated signaling has been implicated in a
variety of cancers, including basal cell carcinoma, glioma and small cell lung cancer. Here, we will focus on the role of
Hh signaling in pancreas development and pancreatic diseases, including diabetes mellitus, chronic pancreatitis and pancreatic
cancer.
Received 5 August 2005; received after revision 4 November 2005; accepted 22 November 2005 相似文献
5.
Kirsten A. Bielefeld Saeid Amini-Nik Benjamin A. Alman 《Cellular and molecular life sciences : CMLS》2013,70(12):2059-2081
Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments. 相似文献
6.
Soluble factors and the development of rod photoreceptors 总被引:7,自引:0,他引:7
Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller
glia, they arise from a population of precursor cells that are multipotent and intrinsic to the retina. Approximately 10 years
ago, several studies demonstrated that retinal precursor cells (RPCs) are competent to respond to environmental factors that
promote cell type determination and differentiation. Since those studies, significant effort has been directed at identifying
the molecular nature of these environmental signals and understanding the precise mechanisms they employ to drive RPCs towards
the different retinal fates. In this review, we describe the recent progress toward understanding how environmental factors
influence the development of vertebrate rod photoreceptors. 相似文献
7.
MAGUKs in synapse assembly and function: an emerging view 总被引:4,自引:0,他引:4
Montgomery JM Zamorano PL Garner CC 《Cellular and molecular life sciences : CMLS》2004,61(7-8):911-929
8.
Bone morphogenetic proteins (BMPs) are one of the main classes of multi-faceted secreted factors that drive vertebrate development. A growing body of evidence indicates that BMPs contribute to the formation of the central nervous system throughout its development, from the initial shaping of the neural primordium to the generation and maturation of the different cell types that form the functional adult nervous tissue. In this review, we focus on the multiple activities of BMPs during spinal cord development, paying particular attention to recent results that highlight the complexity of BMP signaling during this process. These findings emphasize the unique capacity of these signals to mediate various functions in the same tissue throughout development, recruiting diverse effectors and strategies to instruct their target cells. 相似文献
9.
Hedgehog signalling in cancer 总被引:13,自引:0,他引:13
Toftgård R 《Cellular and molecular life sciences : CMLS》2000,57(12):1720-1731
10.
Decoding the Hedgehog signal in animal development 总被引:4,自引:0,他引:4
The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad of developmental processes via a complex signaling
cascade conserved in species ranging from insects to mammals. In many developmental contexts, Hh acts as long-range morphogen
to control distinct cellular outcomes as a function of its concentration. Here we review the current understanding of the
Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal with an emphasis
on the intracellular signaling cascade from the receptor to the nuclear effector. We discuss how graded Hh signals are transduced
to govern distinct developmental outcomes.
Received 28 October 2005; received after revision 6 February 2006; accepted 15 February 2006 相似文献
11.
Comparative studies of the genes involved in sex determination in the three extant classes of mammals, and other vertebrates,
has allowed us to identify genes that are highly conserved in vertebrate sex determination and those that have recently evolved
roles in one lineage. Analysis of the conservation and function of candidate genes in different vertebrate groups has been
crucial to our understanding of their function and positioning in a conserved vertebrate sex-determining pathway. Here we
review comparisons between genes in the sex-determining pathway in different vertebrates, and ask how these comparisons affect
our views on the role of each gene in vertebrate sex determination. 相似文献
12.
From endoderm to pancreas: a multistep journey 总被引:2,自引:0,他引:2
Spagnoli FM 《Cellular and molecular life sciences : CMLS》2007,64(18):2378-2390
The formation of the vertebrate pancreas is a complex process that typifies the basic steps of embryonic development. It involves the establishment of competence, specification, signaling from neighboring tissues, morphogenesis, and the elaboration of tissue-specific genetic networks. A full analysis of this multistep process will help us to understand classic principles of embryonic development. Furthermore, this will provide the blueprint for experimental programming of pancreas formation from embryonic stem cells in the context of diabetes cell-therapy. Although in the past decade many studies have contributed to a solid foundation for understanding pancreatogenesis, important gaps persist in our knowledge of early pancreas formation. This review will summarize the current understanding of the early mechanisms coming into play to pattern the "pre-pancreatic" region within the endoderm and, gradually, specify the pancreatic tissue. 相似文献
13.
The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior–posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal–epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal–epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal–epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration. 相似文献
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Yingqun Wang Herbert Steinbeisser 《Cellular and molecular life sciences : CMLS》2009,66(14):2263-2273
Gastrulation is a crucial step in early embryogenesis. During gastrulation, a set of morphogenetic processes takes place leading
to the establishment of the basic body plan and formation of primary germ layers. A rich body of knowledge about these morphogenetic
processes has been accumulated over decades. The understanding of the molecular mechanism that controls the complex cell movement
and inductive processes during gastrulation remains a challenge. Substantial progress has been made recently to identify and
characterize pathways and molecules implicated in the modulation of morphogenesis during vertebrate gastrulation. Here, we
summarize recent findings in the analysis of signaling pathways implicated in gastrulation movements, with the aim to generalize
the basic molecular principles of vertebrate morphogenesis. 相似文献
16.
Establishment of vertebrate left–right asymmetry is a critical process for normal embryonic development. After the discovery of genes expressed asymmetrically along the left–right axis in chick embryos in the mid 1990s, the molecular mechanisms responsible for left–right patterning in vertebrate embryos have been studied extensively. In this review article, we discuss the mechanisms by which the initial symmetry along the left–right axis is broken in the mouse embryo. We focus on the role of primary cilia and molecular mechanisms of ciliogenesis at the node when symmetry is broken and left–right asymmetry is established. The node is considered a signaling center for early mouse embryonic development, and the results we review here have led to a better understanding of how the node functions and establishes left–right asymmetry. 相似文献
17.
Colorectal carcinoma: from tumorigenesis to treatment 总被引:10,自引:0,他引:10
Colorectal carcinoma (CRC) is a complicated and often fatal genetic disease. Fortunately, owing to rapid expansion of knowledge
and technology development in oncology, much progress has been made regarding the diagnosis, understanding of the molecular
genetics and malignant progression, as well as the novel regimens of CRC. In this review, we summarize the staging system,
the most critical genetic and epigenetic alterations, the pleiotropic effects of MMP-7, the controversial roles of Hedgehog
signaling, the intriguing involvement of thymosin β-4, and the possible contribution of the putative colon (cancer) stem cells
in CRC tumorigenesis. Current treatments as well as several potentially applicable therapeutic strategies for CRC are also
discussed.
Received 15 September 2005; received after revision 3 November 2005; accepted 25 November 2005 相似文献
18.
In vertebrates, internal organs are positioned asymmetrically across the left-right (LR) axis, placing them in a defined area within the body. This LR asymmetric placement is a conserved feature of the vertebrate body plan. Events determining LR asymmetry occur during embryonic development, and are regulated by the coordinated action of genetic mechanisms that are evolutionarily conserved among vertebrates. Recent studies using zebrafish have provided new insights into how the Kupffer's vesicle organizer region is generated, and how it relays LR asymmetry information to the lateral plate mesoderm. In this review, we summarize recent advances in zebrafish and describe our current understanding of the mechanisms underlying these processes. 相似文献
19.
Raber J 《Cellular and molecular life sciences : CMLS》2007,64(6):735-741
Histamine might have an important role in brain development. However, most studies have focused on short-term effects of histamine receptor-mediated signaling on brain function in adulthood. Little is known about the potential long-term effects of histamine receptor-mediated signaling during development on brain function in adulthood. We hypothesize that increased postsynaptic histamine receptor-mediated signaling during development has detrimental effects on brain function in adulthood. Our data support this hypothesis. In the developing mouse brain, histamine H3 receptor blockade, which increases histamine release, has detrimental sex-dependent effects on object recognition, spatial learning in the water maze, and pre-pulse inhibition in adulthood. Our data also support the hypothesis that histamine mediates the detrimental long-term sex-dependent effects of methamphetamine exposure early in life on these brain functions in adulthood. Therefore, increased efforts are warranted to carefully evaluate the effects of drugs that directly or indirectly affect histamine receptor-mediated signaling during development on cognitive function later in life. 相似文献
20.
The vertebrate retina has been widely used as a model to study the development of the central nervous system. Its accessibility and relatively simple organization allow analysis of basic mechanisms such as cell proliferation, differentiation and death. For this reason, it could represent an ideal place to solve the puzzle of Hh signaling during neural development. However, the extensive wealth of data, sometimes apparently discordant, has made the retina one of the most complicated models for studying the role of the Hh cascade. Given the complexity of the field, a deep analysis of the data arising from different animal models is essential. In this review, we will compare and discuss all reported roles of Hh signaling in eye development to shed light on its multiple functions.Received 26 September 2003; received after revision 13 November 2003; accepted 19 November 2003 相似文献