Tumor Microenvironment Promotes Cancer Progression, Metastasis, and Therapeutic Resistance

Sung, Shian Ying; Hsieh, Chia Ling; Wu, Daqing; Chung, Leland W.K.; Johnstone, Peter A.S.

doi:10.1016/j.currproblcancer.2006.12.002

Cited by 96 publications

(79 citation statements)

References 320 publications

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“…These findings suggest that zyxin is involved in TGF-␤1-dependent EMT by regulating cell migration via controlling actin fiber formation. Considering that one of the most important features of EMT is the acquisition of motility (Thiery, 2003;Sung et al, 2007), Zyxin appears to be essential for the progression of EMT. …”

mentioning

confidence: 99%

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

Mori

Nakagami

Koibuchi

et al. 2009

MBoC

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Epithelial-mesenchymal transition (EMT) confers destabilization of cell-cell adhesion and cell motility required for morphogenesis or cancer metastasis. Here we report that zyxin, a focal adhesion-associated LIM protein, is essential for actin reorganization for cell migration in TGF-␤1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-␤1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-␤1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-␤1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-␤1-Twist1-zyxin signal for EMT. Both zyxin and Twist1 were predominantly expressed in the cardiac atrioventricular canal (AVC) that undergoes EMT during heart development. We further performed ex vivo AVC explant assay and revealed that zyxin was required for the reorganization of actin fibers and migration of the endocardial cells. Thus, zyxin reorganizes actin fibers and enhances cell motility in response to TGF-␤1, thereby regulating EMT. INTRODUCTIONEpithelial-mesenchymal transition (EMT) is an essential event during embryogenesis for the formation of many tissues including the mesoderm, for migration of neural crest cells, and for development of the heart valves and septa. The picture emerging from diverse EMT-related studies suggests that precise molecular and cellular control of EMT is complex and context-dependent (Nakaya et al., 2008). An example of developmentally regulated EMT occurs during the initial stages of cardiac morphogenesis. At embryonic day 9.5 (E9.5), endocardial cells undergo EMT ("endocardial EMT"); delaminating from the endothelial sheet, invading the matrix tissue called cardiac jelly, and engaging in endocardial cushion cellularization required for valve and septum formation (Chang et al., 2004). Because a number of congenital heart diseases are caused by abnormal atrioventricular canal (AVC) development (Bruneau, 2008), understanding of the molecular basis of AVC morphogenesis has been long sought, but still not fully achieved. Several EMTinducing transcription factors such as Snail (Cano et al., 2000) and Twist1 (Ma et al., 2005) are expressed in endocardium during development. Although among them, Twist1 is well analyzed as a potent EMT inducer during cancer metastasis (Yang et al., 2004); however, the role for Twist1 in AVC development is not fully understood.An important hallmark of EMT is an increase in cell motility with actin cytoskeletal rearrangement. On EMT induction, the structure of actin cytoskeleton changes dynamically from cortical actin network to stress fiber (Zavadil and Bottinger, 2005). Cell motility also depends on the adhesion of the cell to the substratum where the integrin family molecules bind to the extracellular matrix to form focal adhesion complexes. Stress fibers link the focal adhesion to retract the cells. Furthermore, the nascent focal complexes at the leading edge of the migrating cells are needed for cell crawlin...

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confidence: 99%

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

Mori

Nakagami

Koibuchi

et al. 2009

MBoC

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“…In prostate, tumor cells can induce molecular responses in surrounding stromal cells Finasteride Effects on Prostate Carcinogenesis (46). Reciprocally, activated stromal cells can provide adaptation cues to epithelial cells (46). The epithelial-mesenchymal transition has been proposed as an important means by which epithelial cells respond to signals sent from adjacent stroma (47).…”

Section: Epithelium-stroma Interaction and Accelerated Adaptationmentioning

confidence: 99%

“…In normal prostate, cross-talk between epithelial cells and stromal cells plays an essential role in maintaining tissue homeostasis (46). In prostate, tumor cells can induce molecular responses in surrounding stromal cells Finasteride Effects on Prostate Carcinogenesis (46).…”

Section: Epithelium-stroma Interaction and Accelerated Adaptationmentioning

confidence: 99%

Molecular Profiles of Finasteride Effects on Prostate Carcinogenesis

Kim

2009

Cancer Prevention Research

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Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-α reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.The Prostate Cancer Prevention Trial (PCPT; ref. 1) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (2-5) have shown that 5-α reductase inhibitors are the only agent class proven to be effective in preventing prostate cancer. These positive randomized controlled trials have important implications for understanding the biological potential of the tumor in cases of early prostate cancer as well as for the convergent management (treating and preventing microcancer) of men at a high risk of developing the disease.Morphologically identical prostate tumors can progress at dramatically different rates, and patients in the same cancer risk category can respond very differently to identical treatment. These differences are due in part to the biological heterogeneity of prostate cancer. Some low-risk tumors remain indolent for more than a decade, whereas others rapidly turn deadly. Accurate characterization of the biological potential of the tumor is needed for personalizing prostate cancer treatment. Although the term "risk" commonly connotes the risk of primary prostate cancer, the term is commonly applied in cases of early prostate cancer because of the unusual characteristic of a relatively high frequency of indolent prostate cancer that does not pose a threat of clinical consequences in a patient's lifetime.Categorizing prostate cancer into risk categories (low, intermediate, and high) depends on the available indicators. Prostate cancer patients are stratified into different risk groups and prescribed different treatments based on prostate-specific antigen level, Gleason score (GS), and clinical stage. Common management options for low-or intermediate-risk patients include watchful waiting, prostatectomy, and radiation ther...

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“…Genetic modified viral capsid: Mosaic capsid modifications contain the exogenous insertion introducing the possible interaction with target cells via inserted peptides or large molecules [10,19,32,34,70,87,96,106,114,115] . Among the all applied insertion peptide and molecules, RGD4C is the most popular peptide for viral capsid modification to target the intergrin on the cellular surface majorly expressed on the tumor cells [32,34,54,[87][88][89][90] .…”

Section: Chemical Conjugation Modified Viral Capsidmentioning

confidence: 99%

AAV-Based Targeting Gene Therapy

Shi¹,

Mu²,

Qian³

2008

American J. of Immunology

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Abstract:Since the first parvovirus serotype AAV2 was isolated from human and used as a vector for gene therapy application, there have been significant progresses in AAV vector development. AAV vectors have been extensively investigated in gene therapy for a broad application. AAV vectors have been considered as the first choice of vector due to efficient infectivity, stable expression and nonpathogenicity. However, the untoward events in AAV mediated in vivo gene therapy studies proposed the new challenges for their further applications. Deep understanding of the viral life cycle, viral structure and replication, infection mechanism and efficiency of AAV DNA integration, in terms of contributing viral, host-cell factors and circumstances would promote to evaluate the advantages and disadvantages and provide more insightful information for the possible clinical applications. In this review, main effort will be focused on the recent progresses in gene delivery to the target cells via receptor-ligand interaction and DNA specific integration regulation. Furthermore AAV receptor and virus particle intracellular trafficking are also discussed.

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Tumor Microenvironment Promotes Cancer Progression, Metastasis, and Therapeutic Resistance

Cited by 96 publications

References 320 publications

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

Molecular Profiles of Finasteride Effects on Prostate Carcinogenesis

AAV-Based Targeting Gene Therapy

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