Invading one step at a time: the role of invadopodia in tumor metastasis

Paz, Helicia; Pathak, Navneeta; Yang, Jing

doi:10.1038/onc.2013.393

Cited by 175 publications

(183 citation statements)

References 125 publications

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“…Tks5 long has a mechanistically characterized function in promoting metastasis across a wide variety of cancer types, as it mediates the formation of invadopodia, which are proteolytic membrane protrusions that facilitate cellular invasion (Paz et al 2014). In lung adenocarcinoma, Tks5 long is critical for promoting metastasis, and increased Tks5 long expression correlates with poor patient outcomes (Li et al 2013).…”

Section: Resultsmentioning

confidence: 99%

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Gocheva

Oudin

et al. 2015

Genes Dev.

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Despite the fact that the majority of lung cancer deaths are due to metastasis, the molecular mechanisms driving metastatic progression are poorly understood. Here, we present evidence that loss of Foxa2 and Cdx2 synergizes with loss of Nkx2-1 to fully activate the metastatic program. These three lineage-specific transcription factors are consistently down-regulated in metastatic cells compared with nonmetastatic cells. Knockdown of these three factors acts synergistically and is sufficient to promote the metastatic potential of nonmetastatic cells to that of naturally arising metastatic cells in vivo. Furthermore, silencing of these three transcription factors is sufficient to account for a significant fraction of the gene expression differences between the nonmetastatic and metastatic states in lung adenocarcinoma, including up-regulated expression of the invadopodia component Tks5 long , the embryonal protooncogene Hmga2, and the epithelial-to-mesenchymal mediator Snail. Finally, analyses of tumors from a genetically engineered mouse model and patients show that low expression of Nkx2-1, Foxa2, and Cdx2 strongly correlates with more advanced tumors and worse survival. Our findings reveal that a large part of the complex transcriptional network in metastasis can be controlled by a small number of regulatory nodes that function redundantly, and loss of multiple nodes is required to fully activate the metastatic program.[Keywords: lung adenocarcinoma; metastasis; Nkx2-1; Foxa2; Cdx2; genetically engineered mouse model of cancer] Supplemental material is available for this article.

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Section: Resultsmentioning

confidence: 99%

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Gocheva

Oudin

et al. 2015

Genes Dev.

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“…This process includes two crucial mechanisms: Reduced cell-cell adhesion and ECM degradation (6). ECM degradation is determined by the activity of various proteolytic enzymes, particularly Matrix metalloproteinases (MMPs) (7).…”

Section: Degradation Of the Ecmmentioning

confidence: 99%

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

Zhu

Hu²,

Wei

et al. 2018

Oncol Lett

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Abstract. Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC. Therefore, the molecular mechanisms of LN metastasis in GC development require further investigation. Recently, a large number of clinical studies have focused on the molecular mechanisms and biological markers of tumor invasion and metastasis. However, few articles have broadly summarized LN metastasis in GC, and the molecular mechanisms of LN metastasis are not yet fully understood. In the present review, the molecular mechanisms of LN metastasis in GC will be discussed, including the following aspects: Cell adhesion and movement, ECM degradation, new vessel formation, and molecular pattern differences between metastatic LNs and the primary tumor. This review may lead to a better understanding of LN metastasis in GC, and the identification of new diagnostic markers.

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“…cancer cell lines (30), and evidence shows that invadopodia are associated with invasion and metastasis (31,32). These specialized subcellular structures are activated by cortactin phosphorylation downstream of EGFR stimulation through the activation of Src and Arg kinases and combine focal degradation of the ECM with an actin-dependent protrusion (19,23).…”

Section: Cells Invadopodia Have Been Identified In Numerous Invasivementioning

confidence: 99%

Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway

Glogauer

Sun

Bradley

et al. 2015

Cancer Immunology Research

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Neutrophils have recently been shown to promote invasion and correlate with a poor prognosis in different cancers, including head and neck squamous cell carcinomas. In this study, we analyze the effects of neutrophils in the invasion of oral squamous cell carcinoma (OSCC) using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and UMSCC47 cells (OSCC cell line). Invasion and matrix degradation were determined using a modified in vitro invasion assay and an invadopodia assay, respectively. UMSCC47 and neutrophil cocultures or conditioned media from cocultures increased UMSCC47 invasion, invadopodia formation, and matrix degradation. Further analysis revealed an increase in TNFa and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNFa and IL8 significantly decreased OSCC invasion. Our results show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia and matrix degradation, suggesting a paracrine activation loop between the two cells. Importantly, the presence of neutrophils in the oral environment may modulate the clinical behavior of OSCC.

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Invading one step at a time: the role of invadopodia in tumor metastasis

Cited by 175 publications

References 125 publications

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway

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