Human stem cells alter the invasive properties of somatic cells via paracrine activation of mTORC1.
Nat Commun
; 8(1): 595, 2017 09 19.
Article
in En
| MEDLINE
| ID: mdl-28928383
ABSTRACT
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases. Manipulating the IGF signalling pathway in the context of teratoma formation experiments demonstrates that human stem cells use this mechanism to induce invasion and thereby attract cells from the microenvironment in vivo. In this study we have identified a so far unknown feature of human stem cells, which might play a role for the development of stem cell-derived tumours.Cell invasion is required for several physiological processes but it is unknown if stem cells induce invasiveness in other cells. Here, the authors show that human stem cells secrete insulin-like growth factor, which in turn activates the mTORC1 pathway, initiating invasive behaviour and attracting other cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Teratoma
/
Insulin-Like Growth Factor I
/
Insulin-Like Growth Factor II
/
Carcinoma, Embryonal
/
Paracrine Communication
/
Matrix Metalloproteinases
/
Induced Pluripotent Stem Cells
/
Human Embryonic Stem Cells
/
Mechanistic Target of Rapamycin Complex 1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2017
Type:
Article
Affiliation country:
Austria