NDLI: Phenotypic Diversity of Breast Cancer-Related Mutations in Metalloproteinase-Disintegrin ADAM12

Content Provider	PubMed Central
Author	Yue, Qi Sara, Duhachek-muggy Hui, Li Anna, Zolkiewska
Editor	Hong, Wanjin
Copyright Year	2014
Abstract	Six different somatic missense mutations in the human ADAM12 gene have been identified so far in breast cancer. Five of these mutations involve highly conserved residues in the extracellular domain of the transmembrane ADAM12-L protein. Two of these extracellular mutations, D301H and G479E, have been previously characterized in the context of mouse ADAM12. Three other mutations, T596A, R612Q, and G668A, have been reported more recently, and their effects on ADAM12-L protein structure/function are not known. Here, we show that ADAM12-L bearing the G668A mutation is largely retained in the endoplasmic reticulum in its nascent, full-length form, with an intact N-terminal pro-domain. The T596A and R612Q mutants are efficiently trafficked to the cell surface and proteolytically processed to remove their pro-domains. However, the T596A mutant shows decreased catalytic activity at the cell surface, while the R612Q mutant is fully active and comparable to the wild-type ADAM12-L. The D301H and G479E mutants, consistent with the corresponding D299H and G477E mutants of mouse ADAM12 described earlier, are not proteolytically processed and do not exhibit catalytic activity at the cell surface. Among all six breast cancer-associated mutations in ADAM12-L, mutations that preserve the activity - R612Q and L792F - occur in triple-negative breast cancers, while loss-of-function mutations - D301H, G479E, T596A, and G668A - are found in non-triple negative cancers. This apparent association between the catalytic activity of the mutants and the type of breast cancer supports a previously postulated role of an active ADAM12-L in the triple negative breast cancer disease.
Related Links	http://dx.doi.org/10.1371/journal.pone.0092536
Starting Page	92536
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	3
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-03-20
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Metalloproteinase-disintegrin ADAM12 is associated with a breast tumor-initiating cell phenotype

BREAST CANCER-ASSOCIATED MUTATIONS IN METALLOPROTEASE DISINTEGRIN ADAM12 INTERFERE WITH THE INTRACELLULAR TRAFFICKING AND PROCESSING OF THE PROTEIN

An essential role of metalloprotease-disintegrin ADAM12 in triple-negative breast cancer

A Disintegrin and Metalloproteinase-12 (ADAM12): Function, Roles in Disease Progression, and Clinical Implications

The disintegrin and metalloproteinase ADAM12 contributes to TGF-β signaling through interaction with the type II receptor

ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer

Metalloprotease-disintegrin ADAM12 actively promotes the stem cell-like phenotype in claudin-low breast cancer

The effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression

ADAM12 Induces Estrogen Independence in Breast Cancer Cells

Phenotypic Diversity of Breast Cancer-Related Mutations in Metalloproteinase-Disintegrin ADAM12

Similar Documents

Metalloproteinase-disintegrin ADAM12 is associated with a breast tumor-initiating cell phenotype

BREAST CANCER-ASSOCIATED MUTATIONS IN METALLOPROTEASE DISINTEGRIN ADAM12 INTERFERE WITH THE INTRACELLULAR TRAFFICKING AND PROCESSING OF THE PROTEIN

An essential role of metalloprotease-disintegrin ADAM12 in triple-negative breast cancer

A Disintegrin and Metalloproteinase-12 (ADAM12): Function, Roles in Disease Progression, and Clinical Implications

The disintegrin and metalloproteinase ADAM12 contributes to TGF-β signaling through interaction with the type II receptor

ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer

Metalloprotease-disintegrin ADAM12 actively promotes the stem cell-like phenotype in claudin-low breast cancer

The effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression

ADAM12 Induces Estrogen Independence in Breast Cancer Cells

Phenotypic Diversity of Breast Cancer-Related Mutations in Metalloproteinase-Disintegrin ADAM12