scholarly journals Mutant collagen COL11A1 enhances cancerous invasion

Oncogene ◽  
2021 ◽  
Author(s):  
Carolyn S. Lee ◽  
Zurab Siprashvili ◽  
Angela Mah ◽  
Tomas Bencomo ◽  
Lara E. Elcavage ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Basement Membranes ◽  
The Body ◽  
Β1 Integrin ◽  
Wild Type ◽  
Collagen Genes ◽  
Helical Region

AbstractCollagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of β1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process.

The number of ribosomes on simian virus 40 late 16S mRNA is determined in part by the nucleotide sequence of its leader

1984 ◽  
Vol 4 (4) ◽  
pp. 813-816
Author(s):  
A Barkan ◽  
J E Mertz
Keyword(s):  
Nucleotide Sequence ◽  
Direct Evidence ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
The Body ◽  
Size Distributions ◽  
Wild Type ◽  
Leader Protein ◽  
16S Rna

The size distributions of polyribosomes containing each of three simian virus 40 late 16S mRNA species that differ in nucleotide sequence only within their leaders were determined. The two 16S RNA species with shorter leaders were incorporated into polysomes that were both larger (on average) and narrower in size distribution than was the predominant wild-type 16S RNA. Therefore, the nucleotide sequence of the leader can influence the number of ribosomes present on the body of an mRNA molecule. We propose a model in which the excision from leaders of sizeable translatable regions permits more frequent utilization of internally located translation initiation signals, thereby enabling genes encoded within the bodies of polygenic mRNAs to be translated at higher rates. In addition, the data provide the first direct evidence that VP1 can, indeed, be synthesized in vivo from the species of 16S mRNA that also encodes the 61-amino acid leader protein.

scholarly journals Co-Expression of p16INK4A and Laminin 5 γ2 by Microinvasive and Superficial Squamous Cell Carcinomas in Vivo and by Migrating Wound and Senescent Keratinocytes in Culture

2003 ◽  
Vol 163 (2) ◽  
pp. 477-491 ◽  
Author(s):  
Easwar Natarajan ◽  
Marcela Saeb ◽  
Christopher P. Crum ◽  
Sook B. Woo ◽  
Phillip H. McKee ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Laminin 5

scholarly journals Amniotic fluid fibronectin. Characterization and synthesis by cells in culture.

1978 ◽  
Vol 78 (3) ◽  
pp. 701-715 ◽  
Author(s):  
E Crouch ◽  
G Balian ◽  
K Holbrook ◽  
D Duksin ◽  
P Bornstein
Keyword(s):  
Amniotic Fluid ◽  
Matrix Protein ◽  
Sodium Dodecyl ◽  
Basement Membranes ◽  
The Body ◽  
Connective Tissues ◽  
Human Amniotic Fluid ◽  
Cold Insoluble Globulin ◽  
Kinetics Of

A glycoprotein immunologically related to plasma cold-insoluble globulin (CIG) and fetal skin fibroblast fibronectin has been purified from second-trimester human amniotic fluid. This protein (amniotic fluid fibronectin) migrated more slowly than CIG on sodium dodecyl sulfate gel electrophoresis and showed greater polydispersity which could result, at least in part, from heterogeneity in glycosylation. Cloned human amniotic fluid epithelioid and fibroblastic cells synthesized and secreted a protein with similar properties into the culture medium. Fibronectin was shown to be associated with the pericellular and extracellular matrix of cultured amniotic fluid cells by immunofluorescence, lactoperoxidase-catalyzed iodination, and labeling with ferritin-conjugated antibodies. The kinetics of secretion of the protein were consistent with its role as a matrix protein. We anticipate that amniotic fluid fibronectin will prove to be the same protein which elsewhere in the body is incorporated into connective tissues and basement membranes. Amniotic fluid could, therefore, serve as a convenient source of in vivo synthesized fibronectin for biological and structural studies.

Functional characterization in vivo of mutant p53 molecules derived from squamous cell carcinomas of the head and neck

1997 ◽  
Vol 18 (2) ◽  
pp. 78-88 ◽  
Author(s):  
Massimo Cardinali ◽  
F. James Kratochvil ◽  
John F. Ensley ◽  
Keith C. Robbins ◽  
W. Andrew Yeudall
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Functional Characterization ◽  
Squamous Cell Carcinomas ◽  
Mutant P53

scholarly journals Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells

2008 ◽  
Vol 205 (10) ◽  
pp. 2221-2234 ◽  
Author(s):  
Rachael A. Clark ◽  
Susan J. Huang ◽  
George F. Murphy ◽  
Ilse G. Mollet ◽  
Dirkjan Hijnen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Squamous Cell ◽  
Transforming Growth Factor ◽  
Tumor Regression ◽  
Squamous Cell Carcinomas ◽  
Skin Cancers ◽  
Immune Defects

Squamous cell carcinomas (SCCs) of the skin are sun-induced skin cancers that are particularly numerous in patients on T cell immunosuppression. We found that blood vessels in SCCs did not express E-selectin, and tumors contained few cutaneous lymphocyte antigen (CLA)+ T cells, the cell type thought to provide cutaneous immunosurveillance. Tumors treated with the Toll-like receptor (TLR)7 agonist imiquimod before excision showed induction of E-selectin on tumor vessels, recruitment of CLA+ CD8+ T cells, and histological evidence of tumor regression. SCCs treated in vitro with imiquimod also expressed vascular E-selectin. Approximately 50% of the T cells infiltrating untreated SCCs were FOXP3+ regulatory T (T reg) cells. Imiquimod-treated tumors contained a decreased percentage of T reg cells, and these cells produced less FOXP3, interleukin (IL)-10, and transforming growth factor (TGF)-β. Treatment of T reg cells in vitro with imiquimod inhibited their suppressive activity and reduced FOXP3, CD39, CD73, IL-10, and TGF-β by indirect mechanisms. In vivo and in vitro treatment with imiquimod also induced IL-6 production by effector T cells. In summary, we find that SCCs evade the immune response at least in part by down-regulating vascular E-selectin and recruiting T reg cells. TLR7 agonists neutralized both of these strategies, supporting their use in SCCs and other tumors with similar immune defects.

Sign in / Sign up

Export Citation Format

Share Document