Header

UZH-Logo

Maintenance Infos

The low affinity neurotrophin receptor CD271 regulates phenotype switching in melanoma


Restivo, Gaetana; Diener, Johanna; Cheng, Phil F; Kiowski, Gregor; Bonalli, Mario; Biedermann, Thomas; Reichmann, Ernst; Levesque, Mitchell P; Dummer, Reinhard; Sommer, Lukas (2017). The low affinity neurotrophin receptor CD271 regulates phenotype switching in melanoma. Nature Communications, 8(1):1988.

Abstract

Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic capacity. According to the "phenotype switching" model, the aggressive nature of melanoma cells results from their intrinsic potential to dynamically switch from a high-proliferative/low-invasive to a low-proliferative/high-invasive state. Here we identify the low affinity neurotrophin receptor CD271 as a key effector of phenotype switching in melanoma. CD271 plays a dual role in this process by decreasing proliferation, while simultaneously promoting invasiveness. Dynamic modification of CD271 expression allows tumor cells to grow at low levels of CD271, to reduce growth and invade when CD271 expression is high, and to re-expand at a distant site upon decrease of CD271 expression. Mechanistically, the cleaved intracellular domain of CD271 controls proliferation, while the interaction of CD271 with the neurotrophin receptor Trk-A modulates cell adhesiveness through dynamic regulation of a set of cholesterol synthesis genes relevant for patient survival.

Abstract

Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic capacity. According to the "phenotype switching" model, the aggressive nature of melanoma cells results from their intrinsic potential to dynamically switch from a high-proliferative/low-invasive to a low-proliferative/high-invasive state. Here we identify the low affinity neurotrophin receptor CD271 as a key effector of phenotype switching in melanoma. CD271 plays a dual role in this process by decreasing proliferation, while simultaneously promoting invasiveness. Dynamic modification of CD271 expression allows tumor cells to grow at low levels of CD271, to reduce growth and invade when CD271 expression is high, and to re-expand at a distant site upon decrease of CD271 expression. Mechanistically, the cleaved intracellular domain of CD271 controls proliferation, while the interaction of CD271 with the neurotrophin receptor Trk-A modulates cell adhesiveness through dynamic regulation of a set of cholesterol synthesis genes relevant for patient survival.

Statistics

Citations

Dimensions.ai Metrics
3 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

6 downloads since deposited on 18 Dec 2017
6 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
04 Faculty of Medicine > University Children's Hospital Zurich > Clinic for Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:7 December 2017
Deposited On:18 Dec 2017 14:31
Last Modified:19 Feb 2018 09:35
Publisher:Nature Publishing Group
ISSN:2041-1723
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-017-01573-6
PubMed ID:29215016

Download

Download PDF  'The low affinity neurotrophin receptor CD271 regulates phenotype switching in melanoma'.
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)