TKS5-positive invadopodia-like structures in human tumor surgical specimens

Chen, Yu-Chuan; Baik, Matthew; Byers, Joshua T.; Chen, Kathryn T.; French, Samuel W.; Díaz, Begoña

doi:10.1016/j.yexmp.2018.11.005

Cited by 32 publications

(34 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Emerging evidence demonstrated that invadopodia are essential for cancer cell intravasation ( Gligorijevic et al, 2014 ) and extravasation into specific microenvironments permissive for metastatic colony growth ( Leong et al, 2014 ; Williams et al, 2019 ), as reported in preclinical mouse models, both affecting the efficiency of metastasis. Moreover, results from the analysis of tumor surgical specimens strongly support the existence of invadopodia inside human tumors, further underscoring the clinical relevance of invadopodia for human tumor biology ( Chen Y.C. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 81%

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Masi

Caprara

Bagnato

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

During the metastatic progression, invading cells might achieve degradation and subsequent invasion into the extracellular matrix (ECM) and the underlying vasculature using invadopodia, F-actin-based and force-supporting protrusive membrane structures, operating focalized proteolysis. Their formation is a dynamic process requiring the combined and synergistic activity of ECM-modifying proteins with cellular receptors, and the interplay with factors from the tumor microenvironment (TME). Significant advances have been made in understanding how invadopodia are assembled and how they progress in degradative protrusions, as well as their disassembly, and the cooperation between cellular signals and ECM conditions governing invadopodia formation and activity, holding promise to translation into the identification of molecular targets for therapeutic interventions. These findings have revealed the existence of biochemical and mechanical interactions not only between the actin cores of invadopodia and specific intracellular structures, including the cell nucleus, the microtubular network, and vesicular trafficking players, but also with elements of the TME, such as stromal cells, ECM components, mechanical forces, and metabolic conditions. These interactions reflect the complexity and intricate regulation of invadopodia and suggest that many aspects of their formation and function remain to be determined. In this review, we will provide a brief description of invadopodia and tackle the most recent findings on their regulation by cellular signaling as well as by inputs from the TME. The identification and interplay between these inputs will offer a deeper mechanistic understanding of cell invasion during the metastatic process and will help the development of more effective therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 81%

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Masi

Caprara

Bagnato

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Collectively, these and other findings, support a role for invadopodia in cancer invasiveness and metastatic potential in vivo, and indicate that invadopodia are likely used by cancer cells inside tumors to cross the basement membrane, invade through the stroma and enter the circulation. Consistent with this hypothesis, a subset of TKS5 positive cells is found associated with the leading edge in human pancreatic adenocarcinoma surgical specimens [ 48 ]. A closer look to TKS5-stained cells in pancreatic surgical specimens revealed the presence of invadopodia-like punctate structures, further suggesting that invadopodia are elaborated by cancer cells, including PDAC, inside human tumors [ 48 , 49 , 50 ].…”

Section: Cellular Mechanisms Of Pdac Invasionmentioning

confidence: 72%

“…The long TKS5 isoform (TKS5α) is the prominent form found in cancer cells [ 44 , 45 ], and it is associated with malignant transformation and with poorer prognosis in several human malignancies including glioblastoma and breast cancer [ 41 , 46 , 47 ]. TKS5α is expressed in a number of pancreatic adenocarcinoma cell lines, and TKS5-positive invadopodia are elaborated by the pancreatic cancer cells lines BxPC3 and PANC1 [ 48 , 49 , 50 ] ( Figure 2 ). PDAC cells depleted of TKS5 fail to elaborate invadopodia and degrade gelatin substrates [ 48 ].…”

Section: Cellular Mechanisms Of Pdac Invasionmentioning

confidence: 99%

See 1 more Smart Citation

Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials

et al. 2020

Self Cite

View full text Add to dashboard Cite

Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of PDAC and modulate the reciprocal interactions between cancer and stromal cells in ways that have profound effects in the pathophysiology and treatment of this disease. Here, we review some of the most recent findings regarding the regulation of PDAC cell invasion by the unique microenvironment of this tumor, and how new knowledge is being translated into novel therapeutic approaches.

show abstract

“…If invadopodia have been extensively studied in cell culture, they have now been detected using in situ tissue explants, tissues sections and in vivo models (40). By immunostaining Tks5 on PDAC surgical specimens, Chen et al observed Tks5-positive puncta associated with tumour cells and suggested the presence of invadopodia-like structures inside human tumours (41). Our data strengthen the physiological relevance of invadopodia in PDAC.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin is a structuring component of invadopodia in pancreatic cancer

Dobric

Germain

Bonier

et al. 2020

Preprint

View full text Add to dashboard Cite

Invasion/metastasis axis is the major driver of cancer mortality. By maintaining tissue cohesion, E-cadherin is considered as a protective marker for tumoral progression. However, recent studies suggested that the appearance of hybrid epithelial-mesenchymal (E/M) cells still expressing E-cadherin is favourable for the establishment of metastasis. This hypothesis is consistent with the observation that most pancreatic ductal adenocarcinomas (PDAC) are invasive and express E-cadherin in primary tumour and metastases. By using a data constituted by a series of patient-derived xenografts (PDX) from the PaCaOmics multi-centric clinical trial, we show that E-cadherin expression is not associated with stages of the pathology, prognosis, and overall survival in PDAC. The role of E-cadherin in PDAC aggressiveness was tested both in vitro and in cancer cell implantation models. We show that E-cadherin is a key component of membrane protrusions implicated in the extracellular matrix remodelling and degradation, called invadopodia. E-cadherin downregulation in a pancreatic model of E/M hybrid cells reveals that E-cadherin downregulates Arp2/3 complex expression. As this complex is essential for branched actin structure, E-cadherin depletion strongly impaired invadopodia formation. On the other hand, we demonstrate that E-cadherin interacts with the membrane protease MT1-MMP at the in-vadopodial membrane. E-cadherin could be recycled back to the invadopodial membrane simultaneously with MT1-MMP. Indeed, both Rab7 vesicle-dependant and/or a Rab11 vesicle-dependant pathway are required for both E-cadherin and MT1-MMP trafficking. This new localization of E-cadherin and its implication in cell invasion shines a new light on hybrid EMT features in tumoral invasion.

show abstract

TKS5-positive invadopodia-like structures in human tumor surgical specimens

Cited by 32 publications

References 46 publications

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials

E-cadherin is a structuring component of invadopodia in pancreatic cancer

Contact Info

Product

Resources

About