Special Issue "Cancer Cell Invasion"

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

Deadline for manuscript submissions: closed (30 September 2014)

Special Issue Editor

Guest Editor
Dr. Scott A. Weed (Website)

Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA
Interests: actin cytoskeletal regulation; kinase-based signal transduction; head and neck cancer progression; model systems of squamous cell carcinoma invasion; imaging of cervical lymph node metastasis; carcinogen-induced salivary gland abnormalities

Special Issue Information

Dear Colleagues,

For this issue, we are inviting experts to contribute original research reports and review articles that describe studies in the field of tumor cell invasion. As an essential step in the metastatic cascade, tumor invasion is required for regional and distant cancer cell dissemination. The switch from indolent to invasive neoplasia is complex and varied among different tumor types, but ultimately remains a major root cause underlying the degree of tumor aggressiveness and progression. The extent of invasion in any given cancer directly correlates with poor prognosis and outcomes, where the level of infiltrative involvement with normal tissues complicates patient treatment and management regimes. While different modes and molecular mechanisms have been identified that promote and maintain tumor invasiveness, much remains to be discovered and understood. This is underscored by the unintended promotion of tumor invasion with certain currently utilized targeted therapies, as well as the paucity of therapeutic interventions designed to directly target invasion.

Potential topics include, but are not limited to:

  • Mechanisms involved in breaching restrictive tissue barriers
  • Molecular process that drives tumor cell motility during invasion
  • Regulation of amoeboid and mesenchymal motility modes
  • EMT in tumor invasion
  • Therapeutic targeting of the invasive process
  • Mechanisms of intra- and extravasation

Dr. Scott A. Weed
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).


Keywords

  • invasiveness
  • tumor invasion
  • invadopodia
  • collective invasion
  • ameboid motility
  • tumor intravasation
  • stroma proteolysis
  • EMT in invasion

Published Papers (9 papers)

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Research

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Open AccessArticle Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis
Cancers 2015, 7(1), 342-352; doi:10.3390/cancers7010342
Received: 15 October 2014 / Accepted: 3 February 2015 / Published: 10 February 2015
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Abstract
We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro [...] Read more.
We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessArticle The Roles of Akt Isoforms in the Regulation of Podosome Formation in Fibroblasts and Extracellular Matrix Invasion
Cancers 2015, 7(1), 96-111; doi:10.3390/cancers7010096
Received: 11 October 2014 / Accepted: 22 December 2014 / Published: 7 January 2015
Cited by 3 | PDF Full-text (1672 KB) | HTML Full-text | XML Full-text
Abstract
Mesenchymal cells employ actin-based membrane protrusions called podosomes and invadopodia for cross-tissue migration during normal human development such as embryogenesis and angiogenesis, and in diseases such as atherosclerosis plaque formation and cancer cell metastasis. The Akt isoforms, downstream effectors of phosphatidylinositol 3 [...] Read more.
Mesenchymal cells employ actin-based membrane protrusions called podosomes and invadopodia for cross-tissue migration during normal human development such as embryogenesis and angiogenesis, and in diseases such as atherosclerosis plaque formation and cancer cell metastasis. The Akt isoforms, downstream effectors of phosphatidylinositol 3 kinase (PI3K), play crucial roles in cell migration and invasion, but their involvement in podosome formation and cell invasion is not known. In this study, we have used Akt1 and/or Akt2 knockout mouse embryonic fibroblasts and Akt3-targeted shRNA to determine the roles of the three Akt isoforms in Src and phorbol ester-induced podosome formation, and extracellular matrix (ECM) digestion. We found that deletion or knockdown of Akt1 significantly reduces Src-induced formation of podosomes and rosettes, and ECM digestion, while suppression of Akt2 has little effect. In contrast, Akt3 knockdown by shRNA increases Src-induced podosome/rosette formation and ECM invasion. These data suggest that Akt1 promotes, while Akt3 suppresses, podosome formation induced by Src, and Akt2 appears to play an insignificant role. Interestingly, both Akt1 and Akt3 suppress, while Akt2 enhances, phorbol ester-induced podosome formation. These data show that Akt1, Akt2 and Akt3 play different roles in podosome formation and ECM invasion induced by Src or phorbol ester, thus underscoring the importance of cell context in the roles of Akt isoforms in cell invasion. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)

Review

Jump to: Research

Open AccessReview MLK3 Signaling in Cancer Invasion
Cancers 2016, 8(5), 51; doi:10.3390/cancers8050051
Received: 13 April 2016 / Revised: 5 May 2016 / Accepted: 10 May 2016 / Published: 19 May 2016
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Abstract
Mixed-lineage kinase 3 (MLK3) was first cloned in 1994; however, only in the past decade has MLK3 become recognized as a player in oncogenic signaling. MLK3 is a mitogen-activated protein kinase kinase kinase (MAP3K) that mediates signals from several cell surface receptors [...] Read more.
Mixed-lineage kinase 3 (MLK3) was first cloned in 1994; however, only in the past decade has MLK3 become recognized as a player in oncogenic signaling. MLK3 is a mitogen-activated protein kinase kinase kinase (MAP3K) that mediates signals from several cell surface receptors including receptor tyrosine kinases (RTKs), chemokine receptors, and cytokine receptors. Once activated, MLK3 transduces signals to multiple downstream pathways, primarily to c-Jun terminal kinase (JNK) MAPK, as well as to extracellular-signal-regulated kinase (ERK) MAPK, P38 MAPK, and NF-κB, resulting in both transcriptional and post-translational regulation of multiple effector proteins. In several types of cancer, MLK3 signaling is implicated in promoting cell proliferation, as well as driving cell migration, invasion and metastasis. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches
Cancers 2015, 7(2), 585-597; doi:10.3390/cancers7020585
Received: 17 January 2015 / Revised: 20 March 2015 / Accepted: 24 March 2015 / Published: 31 March 2015
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Abstract
High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution [...] Read more.
High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion
Cancers 2015, 7(1), 382-406; doi:10.3390/cancers7010382
Received: 12 January 2015 / Revised: 10 February 2015 / Accepted: 15 February 2015 / Published: 27 February 2015
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Abstract
Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Extracellular Molecules Involved in Cancer Cell Invasion
Cancers 2015, 7(1), 238-265; doi:10.3390/cancers7010238
Received: 12 December 2014 / Revised: 30 December 2014 / Accepted: 20 January 2015 / Published: 26 January 2015
Cited by 3 | PDF Full-text (942 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved [...] Read more.
Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Desmoglein 3: A Help or a Hindrance in Cancer Progression?
Cancers 2015, 7(1), 266-286; doi:10.3390/cancers7010266
Received: 26 November 2014 / Revised: 9 January 2015 / Accepted: 16 January 2015 / Published: 26 January 2015
Cited by 3 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text
Abstract
Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture [...] Read more.
Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture and structural integrity. Like adherens junctions, desmosomes function as tumour suppressors and are down regulated in the process of epithelial-mesenchymal transition and in tumour cell invasion and metastasis. However, recently several studies have shown that various desmosomal components, including desmoglein 3, are up-regulated in cancer with increased levels of expression correlating with the clinical stage of malignancy, implicating their potentiality to serve as a diagnostic and prognostic marker. Furthermore, in vitro studies have demonstrated that overexpression of desmoglein 3 in cancer cell lines activates several signal pathways that have an impact on cell morphology, adhesion and locomotion. These additional signalling roles of desmoglein 3 may not be associated to its adhesive function in desmosomes but rather function outside of the junctions, acting as a key regulator in the control of actin based cellular processes. This review will discuss recent advances which support the role of desmoglein 3 in cancer progression. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion
Cancers 2015, 7(1), 70-91; doi:10.3390/cancers7010070
Received: 7 October 2014 / Accepted: 23 December 2014 / Published: 30 December 2014
Cited by 11 | PDF Full-text (1114 KB) | HTML Full-text | XML Full-text
Abstract
In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate [...] Read more.
In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFb and highlights how its dysregulation contributes to cancer progression and cell invasion. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)
Open AccessReview Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications
Cancers 2014, 6(4), 2369-2386; doi:10.3390/cancers6042369
Received: 29 September 2014 / Revised: 25 November 2014 / Accepted: 8 December 2014 / Published: 16 December 2014
Cited by 4 | PDF Full-text (804 KB) | HTML Full-text | XML Full-text
Abstract
Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, [...] Read more.
Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. Full article
(This article belongs to the Special Issue Cancer Cell Invasion)

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