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.

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.

CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression

2013 ◽  
Vol 206 (3) ◽  
pp. 418-427 ◽  
Author(s):  
Ming-Chung Jiang ◽  
Chung-Min Yeh ◽  
Cheng-Jeng Tai ◽  
Hung-Chang Chen ◽  
Shu-Hui Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Ras Mutation ◽  
Colorectal Cancer Progression

scholarly journals Collective cancer cell invasion requires RNA accumulation at the invasive front

2020 ◽  
Vol 117 (44) ◽  
pp. 27423-27434 ◽  
Author(s):  
George Chrisafis ◽  
Tianhong Wang ◽  
Konstadinos Moissoglu ◽  
Alexander N. Gasparski ◽  
Yeap Ng ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Single Cells ◽  
Three Dimensional ◽  
Nucleotide Exchange ◽  
Cancer Cell Invasion ◽  
Invasive Front ◽  
Rna Accumulation

Localization of RNAs at protrusive regions of cells is important for single-cell migration on two-dimensional surfaces. Protrusion-enriched RNAs encode factors linked to cancer progression, such as the RAB13 GTPase and the NET1 guanine nucleotide exchange factor, and are regulated by the tumor-suppressor protein APC. However, tumor cells in vivo often do not move as single cells but rather utilize collective modes of invasion and dissemination. Here, we developed an inducible system of three-dimensional (3D) collective invasion to study the behavior and importance of protrusion-enriched RNAs. We find that, strikingly, both theRAB13andNET1RNAs are enriched specifically at the invasive front of leader cells in invasive cell strands. This localization requires microtubules and coincides with sites of high laminin concentration. Indeed, laminin association and integrin engagement are required for RNA accumulation at the invasive front. Importantly, perturbing RNA accumulation reduces collective 3D invasion. Examination of in vivo tumors reveals a similar localization of theRAB13andNET1RNAs at potential invasive sites, suggesting that this mechanism could provide a targeting opportunity for interfering with collective cancer cell invasion.

Functional specificity of Akt isoforms in cancer progression

2011 ◽  
Vol 2 (1-2) ◽  
pp. 1-11 ◽  
Author(s):  
Anne-Marie Fortier ◽  
Eric Asselin ◽  
Monique Cadrin
Keyword(s):  
Tumor Growth ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cancer Cell Invasion ◽  
Akt Inhibitor ◽  
Akt Isoforms ◽  
Specific Localization ◽  
Inhibitor Drug

AbstractAkt/PKB kinases are central mediators of cell homeostasis. There are three highly homologous Akt isoforms, Akt1/PKBα, Akt2/PKBβ and Akt3/PKBγ. Hyperactivation of Akt signaling is a key node in the progression of a variety of human cancer, by modulating tumor growth, chemoresistance and cancer cell migration, invasion and metastasis. It is now clear that, to understand the mechanisms on how Akt affects specific cancer cells, it is necessary to consider the relative importance of each of the three Akt isoforms in the altered cells. Akt1 is involved in tumor growth, cancer cell invasion and chemoresistance and is the predominant altered isoform found in various carcinomas. Akt2 is related to cancer cell invasion, metastasis and survival more than tumor induction. Most of the Akt2 alterations are observed in breast, ovarian, pancreatic and colorectal carcinomas. As Akt3 expression is limited to some tissues, its implication in tumor growth and resistance to drugs mostly occurs in melanomas, gliomas and some breast carcinomas. To explain how Akt isoforms can play different or even opposed roles, three mechanisms have been proposed: tissue-specificity expression/activation of Akt isoforms, distinct effect on same substrate as well as specific localization through the cyto-skeleton network. It is becoming clear that to develop an effective anticancer Akt inhibitor drug, it is necessary to target the specific Akt isoform which promotes the progression of the specific tumor.

scholarly journals Podosomes and Invadopodia: Related structures with Common Protein Components that May Promote Breast Cancer Cellular Invasion

2008 ◽  
Vol 2 ◽  
pp. BCBCR.S789 ◽  
Author(s):  
Daniel C. Flynn ◽  
YoungJin Cho ◽  
Deanne Vincent ◽  
Jess M. Cunnick
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Leading Edge ◽  
Cancer Cell Invasion ◽  
Rate Limiting Step ◽  
Breast Cancer Invasion ◽  
Protein Components ◽  
Compare And Contrast

A rate-limiting step in breast cancer progression is acquisition of the invasive phenotype, which can precede metastasis. Expression of cell-surface proteases at the leading edge of a migrating cell provides cells with a mechanism to cross tissue barriers. A newly appreciated mechanism that may be relevant for breast cancer cell invasion is the formation of invadopodia, well-defined structures that project from the ventral membrane and promote degradation of the extracellular matrix, allowing the cell to cross a tissue barrier. Recently, there has been some controversy and discussion as to whether invadopodia, which are associated with carcinoma cells, are related to a similar structure called podosomes, which are associated with normal cells. Invadopodia and podosomes share many common characteristics, including a similar size, shape, subcellular localization and an ability to promote invasion. These two structures also share many common protein components, which we outline herein. It has been speculated that podosomes may be precursors to invadopodia and by extension both structures may be relevant to cancer cell invasion. Here, we compare and contrast the protein components of invadopodia and podosomes and discuss a potential role for these proteins and the evidence that supports a role for invadopodia and podosomes in breast cancer invasion.

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