Talin2-mediated traction force drives matrix degradation and cell invasion

Qi, Lei; Jafari, Naser; Li, Xiang; Chen, Zaozao; Li, Liqing; Hytönen, Vesa P.; Goult, Benjamin T.; Zhan, Chang‐Guo; Huang, Cai

doi:10.1242/jcs.185959

Cited by 35 publications

(53 citation statements)

References 47 publications

(63 reference statements)

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“…Invasion assays were performed as described [22–24]. Briefly, one hundred microliters of Matrigel (1:30 dilution in serum-free DMEM medium) was added to each Transwell polycarbonate filter (6 mm diameter, 8 μm pore size, Corning) and incubated with the filters at 37°C for 4 hours.…”

Section: Methodsmentioning

confidence: 99%

CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells

et al. 2017

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Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M population. Moreover, NOX4 deficiency resulted in a dramatic decrease in invadopodium formation and the invasive activity. In addition, NOX4 deficiency also caused a decrease in focal adhesions and cell migration in HeLa cells. These results suggest that NOX4 is required for both efficient proliferation and invasion of HeLa cells.

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Section: Methodsmentioning

confidence: 99%

CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells

et al. 2017

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“…For the most part, only talin2 is found at fibrillar adhesions in the centre of the cell 25. This localisation positions talin2 at sites of fibronectin secretion and assembly 32 and also to formation of invadopodia 33. Although much less is known about the role of talin2, it has recently been the subject of increased interest and isoform‐specific functionalities have been reported.…”

Section: The Talinsmentioning

confidence: 99%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

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“…Gelatin Degradation Assays-Gelatin degradation assays were performed as described previously (52). Briefly, glass-bottom dishes were coated with warm Alexa 488-conjugated gelatin (0.2 mg/ml) in PBS containing 2% sucrose.…”

Section: S555amentioning

confidence: 99%

p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion

Jafari

Zheng

et al. 2016

Journal of Biological Chemistry

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Edited by Alex TokerPhosphatidylinositol 4-phosphate 5-kinase type I ␥ (PIPKI␥90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKI␥90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKI␥90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKI␥90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKI␥90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 with Ala promoted PIPKI␥90 ubiquitination but enhanced the stability of PIPKI␥90, and depletion of S6K1 also enhanced the stability of PIPKI␥90, indicating that PIPKI␥90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKI␥90 phosphorylation regulates cell migration and invasion by controlling PIPKI␥90 degradation.Cell migration and invasion are prerequisites for cancer metastasis (1, 2). Thus, the elucidation of the molecular mechanisms of cell migration and invasion is a compelling goal in cancer cell biology.Phosphatidylinositol 4 phosphate 5-kinase type I ␥ (PIPKI␥90) 2 binds talin and localizes to focal adhesions (FAs) (3, 4). It catalyzes ATP-dependent phosphorylation of phosphatidylinositol 4-phosphate (PIP) to generate phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which binds and activates talin, vinculin, and focal adhesion kinase to mediate FA assembly (5, 6). PIP 2 also binds many cytoskeletal proteins, such as neural Wiskott-Aldrich Syndrome protein, gelsolin, and profilin, to regulate actin polymerization (7-10).In addition, PIP 2 is a precursor of several lipid second messengers, such as phosphatidylinositol 3,4,5-triphosphate (PIP 3 ), inositol 1,4,5-triphosphate, and diacylglycerol. We have shown that depletion of PIPKI␥90 completely abolishes PIP 3 production in HCT119 human colon cancer cells (11), indicating a critical role of PIPKI␥90 in lipid signaling. PIPKI␥90 is necessary for epithelial cell adherens junction assembly and progression through the E-cadherin-␤-catenin signal pathway (12). PIPKI␥90 depletion inhibits cell proliferation, MMP9 secretion, and cell motility (13,14). PIPKI␥90 is essential for cell migration, invasion, and metastasis. It is required for focal adhesion assembly and disassembly, key steps in cell migration (11). Depletion of PIPKI␥90 inhibits growth factor-stimulated cell migration in MDA-MB-231 breast cancer cells and HeLa cervical cancer cells (14, 15). PIPKI␥90 knockdown also blocks the invasion of breast cancer and colon cancer cells (11, 16). Furthermore, PIPKI␥90-depleted 4T1 breast cancer cells show significant reduction in tumor progression and metastasis (13). PIPKI␥90 also regulates neutrophil migration by controlling cell polarity as well as rear retraction (17)(18)(19). PIPKI␥90 is a substrate for ...

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Talin2-mediated traction force drives matrix degradation and cell invasion

Cited by 35 publications

References 47 publications

CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells

CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells

The tale of two talins – two isoforms to fine‐tune integrin signalling

p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion

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