scholarly journals New Insight on the Role of Plasminogen Receptor in Cancer Progression

2015 ◽  
Vol 8 ◽  
pp. CGM.S27335 ◽  
Author(s):  
Seema Kumari ◽  
Ramarao Malla
Keyword(s):  
Cancer Progression ◽  
Receptor Gene ◽  
Present Review ◽  
Annexin Ii ◽  
Invasion And Metastasis ◽  
Hairpin Rna ◽  
Diagnostic Strategies ◽  
Surface Receptors ◽  
Interfering Rna

Objective Plasminogen system plays a crucial role in physiological and pathological events related to tissue regeneration, wound healing, immune response, angiogenesis, invasion and metastasis. It gets activated when plasminogen associates with its cell surface receptors. Latest information on some of the well-explored plasminogen receptors such as annexin II-S100A10, cytokeratin 8, α-enolase, plasminogen receptor (KT) (Plg-R(KT)) and histone H2B has been discussed in the present review. These receptors can pave the way for effective new therapeutic and diagnostic strategies to counteract malignant diseases. Conclusion The present review concludes the key role of plasminogen receptors in extracellular matrix degradation, infiltration into surrounding tissues, neovascularization, invasion, metastasis and drug resistance. This review also discusses the possible effect of blocking these plasminogen receptors with monoclonal antibodies and DNA-based vaccination or silencing plasminogen receptor gene using small interfering RNA or short hairpin RNA to counteract cancer invasion and metastasis.

scholarly journals Vimentin filaments drive migratory persistence in polyploidal cancer cells

2020 ◽  
Vol 117 (43) ◽  
pp. 26756-26765
Author(s):  
Botai Xuan ◽  
Deepraj Ghosh ◽  
Joy Jiang ◽  
Rachelle Shao ◽  
Michelle R. Dawson
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Structural Integrity ◽  
Single Cell Analysis ◽  
Critical Role ◽  
Critical Function ◽  
Rna Knockdown ◽  
Interfering Rna ◽  
The Impact

Polyploidal giant cancer cells (PGCCs) are multinucleated chemoresistant cancer cells found in heterogeneous solid tumors. Due in part to their apparent dormancy, the effect of PGCCs on cancer progression has remained largely unstudied. Recent studies have highlighted the critical role of PGCCs as aggressive and chemoresistant cancer cells, as well as their ability to undergo amitotic budding to escape dormancy. Our recent study demonstrated the unique biophysical properties of PGCCs, as well as their unusual migratory persistence. Here we unveil the critical function of vimentin intermediate filaments (VIFs) in maintaining the structural integrity of PGCCs and enhancing their migratory persistence. We performed in-depth single-cell analysis to examine the distribution of VIFs and their role in migratory persistence. We found that PGCCs rely heavily on their uniquely distributed and polarized VIF network to enhance their transition from a jammed to an unjammed state to allow for directional migration. Both the inhibition of VIFs with acrylamide and small interfering RNA knockdown of vimentin significantly decreased PGCC migration and resulted in a loss of PGCC volume. Because PGCCs rely on their VIF network to direct migration and to maintain their enlarged morphology, targeting vimentin or vimentin cross-linking proteins could provide a therapeutic approach to mitigate the impact of these chemoresistant cells in cancer progression and to improve patient outcomes with chemotherapy.

scholarly journals Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Hong-li Jiao ◽  
Bin-shu Weng ◽  
Shan-shan Yan ◽  
Zi-mo Lin ◽  
Shu-yang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Ras Signaling ◽  
Invasion And Metastasis ◽  
In Vivo Models ◽  
Ras Signaling Pathway ◽  
Colorectal Cancer Progression

AbstractOxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A–OSBPL3–RAS axis is a potential target for early therapeutic intervention in CRC progression.

scholarly journals RhoGDIα-dependent balance between RhoA and RhoC is a key regulator of cancer cell tumorigenesis

2011 ◽  
Vol 22 (17) ◽  
pp. 3263-3275 ◽  
Author(s):  
T. T. Giang Ho ◽  
Audrey Stultiens ◽  
Johanne Dubail ◽  
Charles M. Lapière ◽  
Betty V. Nusgens ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Dynamic Balance ◽  
Cellular Functions ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Interfering Rna

RhoGTPases are key signaling molecules regulating main cellular functions such as migration, proliferation, survival, and gene expression through interactions with various effectors. Within the RhoA-related subclass, RhoA and RhoC contribute to several steps of tumor growth, and the regulation of their expression affects cancer progression. Our aim is to investigate their respective contributions to the acquisition of an invasive phenotype by using models of reduced or forced expression. The silencing of RhoC, but not of RhoA, increased the expression of genes encoding tumor suppressors, such as nonsteroidal anti-inflammatory drug–activated gene 1 (NAG-1), and decreased migration and the anchorage-independent growth in vitro. In vivo, RhoC small interfering RNA (siRhoC) impaired tumor growth. Of interest, the simultaneous knockdown of RhoC and NAG-1 repressed most of the siRhoC-related effects, demonstrating the central role of NAG-1. In addition of being induced by RhoC silencing, NAG-1 was also largely up-regulated in cells overexpressing RhoA. The silencing of RhoGDP dissociation inhibitor α (RhoGDIα) and the overexpression of a RhoA mutant unable to bind RhoGDIα suggested that the effect of RhoC silencing is indirect and results from the up-regulation of the RhoA level through competition for RhoGDIα. This study demonstrates the dynamic balance inside the RhoGTPase network and illustrates its biological relevance in cancer progression.

scholarly journals Role of extracellular matrix in breast cancer development: a brief update

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 274 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Jagadeesh Janjanam
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Cancer Development ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Breast Cancer Development ◽  
Cancer Pathogenesis

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

scholarly journals Cell adhesion and urothelial bladder cancer: the role of cadherin switching and related phenomena

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140042 ◽  
Author(s):  
Richard T. Bryan
Keyword(s):  
Bladder Cancer ◽  
Cell Adhesion ◽  
Cancer Progression ◽  
Cell Phenotype ◽  
Urothelial Bladder Cancer ◽  
Invasion And Metastasis ◽  
Cancer Stem Cell Phenotype ◽  
Urothelial Bladder ◽  
Strong Candidate

Cadherins are mediators of cell–cell adhesion in epithelial tissues. E-cadherin is a known tumour suppressor and plays a central role in suppressing the invasive phenotype of cancer cells. However, the abnormal expression of N- and P-cadherin (‘cadherin switching’, CS) has been shown to promote a more invasive and m̀alignant phenotype of cancer, with P-cadherin possibly acting as a key mediator of invasion and metastasis in bladder cancer. Cadherins are also implicated in numerous signalling events related to embryonic development, tissue morphogenesis and homeostasis. It is these wide ranging effects and the serious implications of CS that make the cadherin cell adhesion molecules and their related pathways strong candidate targets for the inhibition of cancer progression, including bladder cancer. This review focuses on CS in the context of bladder cancer and in particular the switch to P-cadherin expression, and discusses other related molecules and phenomena, including EpCAM and the development of the cancer stem cell phenotype.

scholarly journals The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4720
Author(s):  
Paris Jabeen Asif ◽  
Ciro Longobardi ◽  
Michael Hahne ◽  
Jan Paul Medema
Keyword(s):  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cancer Invasion ◽  
Cancer Associated Fibroblasts ◽  
Targeted Therapeutics ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Future Studies

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

scholarly journals The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1772
Author(s):  
Alamelu G. Bharadwaj ◽  
Emma Kempster ◽  
David M. Waisman
Keyword(s):  
Cell Surface ◽  
Cancer Cells ◽  
Proteolytic Activity ◽  
Cancer Progression ◽  
Tumor Development ◽  
Surface Receptors ◽  
Diagnosis And Prognosis ◽  
Physiological Processes ◽  
Complex Regulation

The generation of the serine protease plasmin is initiated by the binding of its zymogenic precursor, plasminogen, to cell surface receptors. The proteolytic activity of plasmin, generated at the cell surface, plays a crucial role in several physiological processes, including fibrinolysis, angiogenesis, wound healing, and the invasion of cells through both the basement membrane and extracellular matrix. The seminal observation by Albert Fischer that cancer cells, but not normal cells in culture, produce large amounts of plasmin formed the basis of current-day observations that plasmin generation can be hijacked by cancer cells to allow tumor development, progression, and metastasis. Thus, the cell surface plasminogen-binding receptor proteins are critical to generating plasmin proteolytic activity at the cell surface. This review focuses on one of the twelve well-described plasminogen receptors, S100A10, which, when in complex with its regulatory partner, annexin A2 (ANXA2), forms the ANXA2/S100A10 heterotetrameric complex referred to as AIIt. We present the theme that AIIt is the quintessential cellular plasminogen receptor since it regulates the formation and the destruction of plasmin. We also introduce the term oncogenic plasminogen receptor to define those plasminogen receptors directly activated during cancer progression. We then discuss the research establishing AIIt as an oncogenic plasminogen receptor-regulated during EMT and activated by oncogenes such as SRC, RAS, HIF1α, and PML-RAR and epigenetically by DNA methylation. We further discuss the evidence derived from animal models supporting the role of S100A10 in tumor progression and oncogenesis. Lastly, we describe the potential of S100A10 as a biomarker for cancer diagnosis and prognosis.

scholarly journals Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity

2020 ◽  
Vol 68 (12) ◽  
pp. 871-885 ◽  
Author(s):  
Athanasios Papadas ◽  
Garrett Arauz ◽  
Alexander Cicala ◽  
Joshua Wiesner ◽  
Fotis Asimakopoulos
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Immune Cell ◽  
Invasion And Metastasis ◽  
Tissue Invasion ◽  
Immune Biomarkers ◽  
Cancer Inflammation ◽  
Proliferative Signaling ◽  
Growth Suppressor

Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies. This article summarizes work from several laboratories, including ours, on the role of this central matrix proteoglycan in tumor progression as well as tumor-immune cell cross-talk:

scholarly journals Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3793
Author(s):  
Katyana Amilca-Seba ◽  
Michèle Sabbah ◽  
Annette K. Larsen ◽  
Jérôme A. Denis
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Clinical Applications ◽  
Invasion And Metastasis ◽  
Clinical Laboratories ◽  
Clinical Biomarker ◽  
Colorectal Cancer Progression ◽  
Routine Assay ◽  
Tumor Types

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.

scholarly journals Role of extracellular matrix in breast cancer development: a brief update

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 274 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Jagadeesh Janjanam
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Cancer Development ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Breast Cancer Development ◽  
Cancer Pathogenesis

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

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