TGF beta-induced changes in membrane curvature influence Ras oncoprotein membrane localization

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00560339" target="_blank" >RIV/68378050:_____/22:00560339 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-022-17482-8" target="_blank" >https://www.nature.com/articles/s41598-022-17482-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-022-17482-8" target="_blank" >10.1038/s41598-022-17482-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

TGF beta-induced changes in membrane curvature influence Ras oncoprotein membrane localization

Popis výsledku v původním jazyce

In the course of cancer progression tumor cells undergo morphological changes that lead to increased motility and invasiveness thus promoting formation of metastases. This process called epithelial to mesenchymal transition (EMT) is triggered by transforming growth factor (TGF beta) but for gaining the full invasive potential an interplay between signaling of TGF beta and Ras GTPases is required. Ras proteins possess a lipidated domain that mediates Ras association with the plasma membrane, which is essential for Ras biological functions. Type and number of the lipid anchors are the main difference among three Ras variants-H-ras, N-ras and K-ras. The lipid anchors determine membrane partitioning of lipidated proteins into membrane areas of specific physico-chemical properties and curvature. In this study, we investigated the effect of TGF beta treatment on the subcellular localization of H-ras and K-ras. We show that TGF beta increases positive plasma membrane curvature, which is subsequently sensed by H-ras, leading to its elevated plasma membrane localization and activation. This observation suggests the existence of a novel positive feedback loop whereby the increased level of plasma membrane curvature during TGF beta induced EMT attracts more Ras molecules to the plasma membrane resulting in increased Ras activity which in turn promotes further EMT and thus ultimately enables the acquisition of full invasive potential.

Název v anglickém jazyce

TGF beta-induced changes in membrane curvature influence Ras oncoprotein membrane localization

Popis výsledku anglicky

In the course of cancer progression tumor cells undergo morphological changes that lead to increased motility and invasiveness thus promoting formation of metastases. This process called epithelial to mesenchymal transition (EMT) is triggered by transforming growth factor (TGF beta) but for gaining the full invasive potential an interplay between signaling of TGF beta and Ras GTPases is required. Ras proteins possess a lipidated domain that mediates Ras association with the plasma membrane, which is essential for Ras biological functions. Type and number of the lipid anchors are the main difference among three Ras variants-H-ras, N-ras and K-ras. The lipid anchors determine membrane partitioning of lipidated proteins into membrane areas of specific physico-chemical properties and curvature. In this study, we investigated the effect of TGF beta treatment on the subcellular localization of H-ras and K-ras. We show that TGF beta increases positive plasma membrane curvature, which is subsequently sensed by H-ras, leading to its elevated plasma membrane localization and activation. This observation suggests the existence of a novel positive feedback loop whereby the increased level of plasma membrane curvature during TGF beta induced EMT attracts more Ras molecules to the plasma membrane resulting in increased Ras activity which in turn promotes further EMT and thus ultimately enables the acquisition of full invasive potential.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

13486

Kód UT WoS článku

000836707300054

EID výsledku v databázi Scopus

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