scholarly journals Cancer Invasion: Patterns and Mechanisms

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 17-28 ◽  
Author(s):  
N. V. Krakhmal ◽  
M. V. Zavyalova ◽  
E. V. Denisov ◽  
S. V. Vtorushin ◽  
V. M. Perelmuter
Keyword(s):  
Cell Migration ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Cancer Invasion ◽  
Collective Cell Migration ◽  
Cancer Cell Migration ◽  
Cancer Cell Invasion ◽  
Invasion Patterns

Cancer invasion and the ability of malignant tumor cells for directed migration and metastasis have remained a focus of research for many years. Numerous studies have confirmed the existence of two main patterns of cancer cell invasion: collective cell migration and individual cell migration, by which tumor cells overcome barriers of the extracellular matrix and spread into surrounding tissues. Each pattern of cell migration displays specific morphological features and the biochemical/molecular genetic mechanisms underlying cell migration. Two types of migrating tumor cells, mesenchymal (fibroblast-like) and amoeboid, are observed in each pattern of cancer cell invasion. This review describes the key differences between the variants of cancer cell migration, the role of epithelial-mesenchymal, collective-amoeboid, mesenchymal-amoeboid, and amoeboid-mesenchymal transitions, as well as the significance of different tumor factors and stromal molecules in tumor invasion. The data and facts collected are essential to the understanding of how the patterns of cancer cell invasion are related to cancer progression and therapy efficacy. Convincing evidence is provided that morphological manifestations of the invasion patterns are characterized by a variety of tissue (tumor) structures. The results of our own studies are presented to show the association of breast cancer progression with intratumoral morphological heterogeneity, which most likely reflects the types of cancer cell migration and results from different activities of cell adhesion molecules in tumor cells of distinct morphological structures.

scholarly journals Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

2021 ◽  
Author(s):  
Alessandra Toti ◽  
Alice Santi ◽  
Elisa Pardella ◽  
Ilaria Nesi ◽  
Richard Tomasini ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tumor Stroma ◽  
Activation Process ◽  
Cancer Cell Migration ◽  
Stromal Compartment ◽  
Activated Fibroblasts

AbstractCancer-associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF-derived MVs changes the overall protein content of tumor cells. In this paper, we demonstrate that tumor activated fibroblasts overexpress Galectin-1 (Gal-1) and consequently release MVs containing increased levels of this protein. The uptake of Gal-1 enriched MVs by tumor cells leads to the upregulation of its intracellular concentration, that strongly affects cancer cell migration, while neither proliferation nor adhesion are altered. Accordingly, tumor cells co-cultured with fibroblasts silenced for Gal-1 have a reduced migratory ability. The present work reveals the key role of an exogenous protein, Gal-1, derived from activated fibroblasts, in cancer progression, and contributes to clarify the importance of MVs-mediated protein trafficking in regulating tumor-stroma crosstalk.

scholarly journals TP53 drives invasion through expression of its Δ133p53β variant

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Gilles Gadea ◽  
Nikola Arsic ◽  
Kenneth Fernandes ◽  
Alexandra Diot ◽  
Sébastien M Joruiz ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Tp53 Mutation ◽  
P53 Protein ◽  
Clinical Analysis ◽  
Breast Cancer Patients ◽  
Cancer Cell Invasion ◽  
Mutation Status ◽  
Risk Of Cancer

TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.

Autophagic stress; a new cellular response to nanoparticles. Could it be a new strategy for inhibition of liver cancer cell invasion and metastasis?

Nanoscale ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 6556-6561 ◽  
Author(s):  
Chalermchai Pilapong ◽  
Thipjutha Phatruengdet ◽  
Saowalak Krungchanuchat
Keyword(s):  
Liver Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cellular Response ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Liver Cancer Cell ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
New Strategy

The autophagic stress induced by Fe–TA NPs is capable of reducing liver cancer cell migration and invasion. This would be a new tactic to treat liver cancer.

uPAR and mTORC2 as coupled targets for therapeutics development in bladder cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 447-447
Author(s):  
Andrew M. Hau ◽  
Andrew Gilder ◽  
Jing-jing Hu ◽  
Steven L. Gonias ◽  
Donna E. Hansel
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Invasive Bladder Cancer ◽  
Migration And Invasion ◽  
Cancer Cell Invasion ◽  
Cell Migration And Invasion

447 Background: Bladder cancer currently ranks as the fifth most common and the single most expensive cancer to manage in the United States. Although it is established that invasive behavior is a major predictor of diminished outcomes for patients with bladder cancer, the molecular mechanisms governing bladder cancer cell invasion are not well understood. The urokinase receptor (uPAR) and mammalian target of rapamycin complex 2 (mTORC2) represent two powerful pro-invasion candidates that have increased expression in high-grade, invasive bladder cancer, though the former has not been characterized in detail in bladder cancer. Therefore, the aims of this study are to characterize the uPAR signaling network and delineate the signaling interplay between mTORC2 and uPAR in bladder cancer. Methods: Using immunoblot and RT-qPCR analyses, we evaluated uPAR expression in a panel of immortalized bladder cancer cell lines: UROtsa, RT4, UMUC3, T24 and J82. uPAR influence on mTORC1 and mTORC2 signaling was determined by immunoblot analysis following targeted gene-silencing of uPAR using siRNA. Additionally, the effects of uPAR knockdown on cell migration and invasion were investigated using modified scratch-wound migration and transwell invasion assays. Lastly, signaling interplay between uPAR and mTORC2 was investigated by evaluating the effects of uPAR and mTORC2 silencing on Rac1 activity. Results: uPAR knockdown in a subset (T24 and J82) of invasive bladder cancer cell lines inhibited mTORC2, but not mTORC1, activity as measured by P-AKT S473 and P-S6 levels. We found that uPAR silencing in T24 and J82 cells resulted in significant reductions in cell migration and invasion through Matrigel. This is likely attributed to inhibition of Rac1 and decreased lamellipodia formation. Conclusions: Collectively, our results identify uPAR and mTORC2 as major regulators of bladder cancer cell invasion and that these two systems are linked through Rac1. Further investigation of uPAR and mTORC2 inhibition using uPAR-targeting antibodies and mTOR inhibitors in an in vivo mouse model of bladder cancer will determine if these signaling pathways are therapeutically beneficial for the treatment of bladder cancer.

scholarly journals Markers of Cancer Cell Invasion: Are They Good Enough?

2019 ◽  
Vol 8 (8) ◽  
pp. 1092 ◽  
Author(s):  
Tatiana S. Gerashchenko ◽  
Nikita M. Novikov ◽  
Nadezhda V. Krakhmal ◽  
Sofia Y. Zolotaryova ◽  
Marina V. Zavyalova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Cancer Cell Invasion ◽  
Mesenchymal Transition ◽  
Morphological Heterogeneity ◽  
Extracellular Matrix Components

Invasion, or directed migration of tumor cells into adjacent tissues, is one of the hallmarks of cancer and the first step towards metastasis. Penetrating to adjacent tissues, tumor cells form the so-called invasive front/edge. The cellular plasticity afforded by different kinds of phenotypic transitions (epithelial–mesenchymal, collective–amoeboid, mesenchymal–amoeboid, and vice versa) significantly contributes to the diversity of cancer cell invasion patterns and mechanisms. Nevertheless, despite the advances in the understanding of invasion, it is problematic to identify tumor cells with the motile phenotype in cancer tissue specimens due to the absence of reliable and acceptable molecular markers. In this review, we summarize the current information about molecules such as extracellular matrix components, factors of epithelial–mesenchymal transition, proteases, cell adhesion, and actin cytoskeleton proteins involved in cell migration and invasion that could be used as invasive markers and discuss their advantages and limitations. Based on the reviewed data, we conclude that future studies focused on the identification of specific invasive markers should use new models one of which may be the intratumor morphological heterogeneity in breast cancer reflecting different patterns of cancer cell invasion.

scholarly journals Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yinghui Ren ◽  
Limin Cao ◽  
Limin Wang ◽  
Sijia Zheng ◽  
Qicheng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Small Cell ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Invasion ◽  
Lung Cancer Cell ◽  
Small Cell Lung

AbstractTumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Here, we reported that autophagy was upregulated in lung cancer-associated CAFs compared to normal fibroblasts (NFs), and autophagy was responsible for the promoting effect of CAFs on non-small cell lung cancer (NSCLC) cell migration and invasion. Inhibition of CAFs autophagy attenuated their regulation on epithelial–mesenchymal transition (EMT) and metastasis-related genes of NSCLC cells. High mobility group box 1 (HMGB1) secreted by CAFs mediated CAFs’ effect on lung cancer cell invasion, demonstrated by using recombinant HMGB1, HMGB1 neutralizing antibody, and HMGB1 inhibitor glycyrrhizin (GA). Importantly, the autophagy blockade of CAFs revealed that HMGB1 release was dependent on autophagy. We also found HMGB1 was responsible, at least in part, for autophagy activation of CAFs, suggesting CAFs remain active through an autocrine HMGB1 loop. Further study demonstrated that HMGB1 facilitated lung cancer cell invasion by activating the NFκB pathway. In a mouse xenograft model, the autophagy specific inhibitor chloroquine abolished the stimulating effect of CAFs on tumor growth. These results elucidated an oncogenic function for secretory autophagy in lung cancer-associated CAFs that promotes metastasis potential, and suggested HMGB1 as a novel therapeutic target.

scholarly journals O-GlcNAcylation of MORC2 at threonine 556 by OGT couples TGF-β signaling to breast cancer progression

2022 ◽  
Author(s):  
Ying-Ying Liu ◽  
Hong-Yi Liu ◽  
Tian-Jian Yu ◽  
Qin Lu ◽  
Fang-Lin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Tgf Β1

AbstractMORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme involved in DNA damage response and gene transcription, and its dysregulation has been linked with Charcot-Marie-Tooth disease, neurodevelopmental disorder, and cancer. Despite its functional importance, how MORC2 is regulated remains enigmatic. Here, we report that MORC2 is O-GlcNAcylated by O-GlcNAc transferase (OGT) at threonine 556. Mutation of this site or pharmacological inhibition of OGT impairs MORC2-mediated breast cancer cell migration and invasion in vitro and lung colonization in vivo. Moreover, transforming growth factor-β1 (TGF-β1) induces MORC2 O-GlcNAcylation through enhancing the stability of glutamine-fructose-6-phosphate aminotransferase (GFAT), the rate-limiting enzyme for producing the sugar donor for OGT. O-GlcNAcylated MORC2 is required for transcriptional activation of TGF-β1 target genes connective tissue growth factor (CTGF) and snail family transcriptional repressor 1 (SNAIL). In support of these observations, knockdown of GFAT, SNAIL or CTGF compromises TGF-β1-induced, MORC2 O-GlcNAcylation-mediated breast cancer cell migration and invasion. Clinically, high expression of OGT, MORC2, SNAIL, and CTGF in breast tumors is associated with poor patient prognosis. Collectively, these findings uncover a previously unrecognized mechanistic role for MORC2 O-GlcNAcylation in breast cancer progression and provide evidence for targeting MORC2-dependent breast cancer through blocking its O-GlcNAcylation.

Sign in / Sign up

Export Citation Format

Share Document