Impact of collagen triple helix structure on melanoma cell invadopodia formation and matrix degradation upon BRAF inhibitor treatment

The effect of glycine-to-arginine mutations in the alpha 1 (I)-chain on collagen triple-helix structure in lethal perinatal osteogenesis imperfecta was studied by determination of the helix denaturation temperature and by computerized molecular modelling. Arginine substitutions at glycine residues 391 and 667 resulted in similar small decreases in helix stability. Molecular modelling suggested that the glycine-to-arginine-391 mutant resulted in only a relatively small localized disruption to the helix structure. Thus the glycine-to-arginine substitutions may lead to only a small structural abnormality of the collagen helix, and it is most likely that the over-modification of lysine, poor secretion, increased degradation and other functional sequelae result from a kinetic defect in collagen helix formation resulting from the mutation.

Download Full-text

Recent Progress on Collagen Triple Helix Structure, Stability and Assembly

Protein and Peptide Letters ◽

10.2174/0929866023408922 ◽

2002 ◽

Vol 9 (2) ◽

pp. 107-116 ◽

Cited By ~ 36

Author(s):

Rita Berisio ◽

Luigi Vitagliano ◽

Lelio Mazzarella ◽

Adriana Zagari

Keyword(s):

Triple Helix ◽

Recent Progress ◽

Structure Stability ◽

Collagen Triple Helix ◽

Helix Structure

Download Full-text

Unraveling the Role of Hydroxyproline in Maintaining the Thermal Stability of the Collagen Triple Helix Structure Using Simulation

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.9b05006 ◽

2019 ◽

Vol 123 (36) ◽

pp. 7754-7763 ◽

Cited By ~ 1

Author(s):

Songcheng Xu ◽

Min Gu ◽

Kun Wu ◽

Guoying Li

Keyword(s):

Thermal Stability ◽

Triple Helix ◽

Collagen Triple Helix ◽

Helix Structure ◽

Thermal Stability Of

Download Full-text

Faculty Opinions recommendation of Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)(10)](3).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004876.56455 ◽

2002 ◽

Author(s):

Patricia C Weber

Keyword(s):

Crystal Structure ◽

Triple Helix ◽

Collagen Triple Helix ◽

Triple Helix Model

Download Full-text

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Cells ◽

10.3390/cells10020388 ◽

2021 ◽

Vol 10 (2) ◽

pp. 388

Author(s):

Brice Chanez ◽

Kevin Ostacolo ◽

Ali Badache ◽

Sylvie Thuault

Keyword(s):

Breast Cancer ◽

Cancer Cell ◽

Cell Invasion ◽

Focal Adhesions ◽

Matrix Degradation ◽

Cancer Cell Invasion ◽

Wild Type ◽

Spatial Regulation ◽

Invadopodia Formation

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

Download Full-text

The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms22052426 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2426

Author(s):

Askhat Myngbay ◽

Limara Manarbek ◽

Steve Ludbrook ◽

Jeannette Kunz

Keyword(s):

Rheumatoid Arthritis ◽

Drug Targets ◽

Triple Helix ◽

Cancer Metastasis ◽

Bone Erosion ◽

Cartilage Destruction ◽

Patient Treatment ◽

Collagen Triple Helix ◽

Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

Download Full-text

A neutral polysaccharide with a triple helix structure from ginger: Characterization and immunomodulatory activity

Food Chemistry ◽

10.1016/j.foodchem.2021.129261 ◽

2021 ◽

Vol 350 ◽

pp. 129261

Author(s):

Xiaolong Yang ◽

Siqing Wei ◽

Xiaoming Lu ◽

Xuguang Qiao ◽

Jesus Simal-Gandara ◽

...

Keyword(s):

Triple Helix ◽

Immunomodulatory Activity ◽

Helix Structure

Download Full-text

The phosphatase Shp1 interacts with and dephosphorylates cortactin to inhibit invadopodia function

Cell Communication and Signaling ◽

10.1186/s12964-021-00747-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alessia Varone ◽

Chiara Amoruso ◽

Marcello Monti ◽

Manpreet Patheja ◽

Adelaide Greco ◽

...

Keyword(s):

Extracellular Matrix ◽

Tyrosine Phosphatase ◽

Melanoma Cells ◽

Matrix Degradation ◽

Extracellular Matrix Degradation ◽

Invadopodia Formation ◽

Interference Rna

Abstract Background Invadopodia are actin-based cell-membrane protrusions associated with the extracellular matrix degradation accompanying cancer invasion. The elucidation of the molecular mechanisms leading to invadopodia formation and activity is central for the prevention of tumor spreading and growth. Protein tyrosine kinases such as Src are known to regulate invadopodia assembly, little is however known on the role of protein tyrosine phosphatases in this process. Among these enzymes, we have selected the tyrosine phosphatase Shp1 to investigate its potential role in invadopodia assembly, due to its involvement in cancer development. Methods Co-immunoprecipitation and immunofluorescence studies were employed to identify novel substrate/s of Shp1AQ controlling invadopodia activity. The phosphorylation level of cortactin, the Shp1 substrate identified in this study, was assessed by immunoprecipitation, in vitro phosphatase and western blot assays. Short interference RNA and a catalytically-dead mutant of Shp1 expressed in A375MM melanoma cells were used to evaluate the role of the specific Shp1-mediated dephosphorylation of cortactin. The anti-invasive proprieties of glycerophosphoinositol, that directly binds and regulates Shp1, were investigated by extracellular matrix degradation assays and in vivo mouse model of metastasis. Results The data show that Shp1 was recruited to invadopodia and promoted the dephosphorylation of cortactin at tyrosine 421, leading to an attenuated capacity of melanoma cancer cells to degrade the extracellular matrix. Controls included the use of short interference RNA and catalytically-dead mutant that prevented the dephosphorylation of cortactin and hence the decrease the extracellular matrix degradation by melanoma cells. In addition, the phosphoinositide metabolite glycerophosphoinositol facilitated the localization of Shp1 at invadopodia hence promoting cortactin dephosphorylation. This impaired invadopodia function and tumor dissemination both in vitro and in an in vivo model of melanomas. Conclusion The main finding here reported is that cortactin is a specific substrate of the tyrosine phosphatase Shp1 and that its phosphorylation/dephosphorylation affects invadopodia formation and, as a consequence, the ability of melanoma cells to invade the extracellular matrix. Shp1 can thus be considered as a regulator of melanoma cell invasiveness and a potential target for antimetastatic drugs.

Download Full-text