Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion

By Katarina Wolf, Yi I. Wu, Yueying Liu, J. Geiger, E. Tam, Christopher M. Overall, M. Stack, Peter Friedl. Nature Cell Biology, 2007

1,033 citations recorded by the source corpus.

Invasive cell migration through tissue barriers requires pericellular remodelling of extracellular matrix (ECM) executed by cell-surface proteases, particularly membrane-type-1 matrix metalloproteinase (MT1-MMP/MMP-14). Using time-resolved multimodal microscopy, we show how invasive HT-1080 fibrosarcoma and MDA-MB-231 breast cancer cells coordinate mechanotransduction and fibrillar collagen remodelling by segregating the anterior force-generating leading edge containing β1 integrin, MT1-MMP and F-actin from a posterior proteolytic zone executing fibre breakdown. During forward movement, sterically impeding fibres are selectively realigned into microtracks of single-cell calibre. Microtracks become expanded by multiple following cells by means of the large-scale degradation of lateral ECM interfaces, ultimately prompting transition towards collective invasion similar to that in vivo. Both ECM track widening and transition to multicellular invasion are dependent on MT1-MMP-mediated collagenolysis, shown by broad-spectrum protease inhibition and RNA interference. Thus, invasive migration and proteolytic ECM remodelling are interdependent processes that control tissue micropatterning and macropatterning and, consequently, individual and collective cell migration.

Subfields: Cancer Research, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/257d3c450aff707ca9bb00c0edbbd52da108bdab

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Valerie M. Weaver
2. Zena Werb
3. Peter Friedl
4. M. Egeblad
5. Raghu Kalluri
6. J. Erler
7. Erik Sahai
8. V. Plaks

In Cell Biology

1. Peter Friedl
2. Valerie M. Weaver
3. Zena Werb
4. R. Grosse
5. Erik Sahai
6. J. Erler
7. D. Gilmour
8. Sanjay Kumar

In Immunology and Allergy

1. Valerie M. Weaver
2. Peter Friedl
3. Zena Werb
4. R. Grosse
5. Erik Sahai
6. Sanjay Kumar
7. M. Egeblad
8. J. Lammerding

Citations in the corpus

• The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function (2011, neutral): “Collective cell migration requires the MT1MMP-mediated degradation of collagen to generate the ECM tracks through which these groups of cells mov”
• Rho GTPases in cancer cell biology (2008, neutral): “migration to another depending on conditions [17,18].”
• Matrix Metalloproteinases: Regulators of the Tumor Microenvironment (2010, background): “A striking observation is that metastatic cancer cells can switch from a protease-dependent to a protease-independent invasion program by utilizing an amoeboid migration mode (Wolf et al., 2007).”
• Systems Biology of Cancer Metastasis (2019, background): “…from the primary tumor mass(Aceto et al., 2014; Massague and Obenauf, 2016; Ye et al., 2015; Yu et al., 2013), and that these programs are both cell intrinsic(Alexander et al., 2008), and triggered in response to the extracellular microenvironment(Hofschroer et al., 2017; Wolf et al., 2007).”
• Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells (2007, background): “A recent study has shown that MT1-MMP (MMP14) is required to mediate matrix proteolysis during collective invasion; however, this study used cells that were either of mesenchymal origin (HT1080) or had upregulated mesenchymal markers (MDA-MB-231”
• Mechanotransduction gone awry (2009, background): “In the past decade, sudden changes in ECM mechanics, ECM remodelling and the resultant disturbance in cytoskeletal tension and mechanotransduction signalling have emerged as important factors that can promote malignant transformation, tumorigenesis and metastasi”
• Mechanics, malignancy, and metastasis: The force journey of a tumor cell (2009, methodology): “This process was recently captured in real time through elegant multimodal dynamic imaging conducted by Wolf, Friedl, and colleagues [27].”
• Dynamic interplay between the collagen scaffold and tumor evolution (2010, background): “Proteolysis of the ECM generates pathways for cells to migrate through [50-53].”
• Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin signaling (2009, background): “This suggests that other factors that modulate integrins and/or ECM remodeling or cellular tension likely cooperate with ECM crosslinking and force to promote tumor invasion (Katz et al., 2007; Wolf et al., 2007).”