Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL

Maria Pelullo, Roberta Quaranta, Claudio Talora, Saula Checquolo, Samantha Cialfi, Maria P ia Felli, Geertruy te Kronnie, Chiara Borga, Zein M ersini Besharat, Rocco Palermo, Lucia Di Marcotullio, Anthony J Capobianco, Alberto Gulino, Isabella Screpanti, Diana Bellavia

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Deregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL). Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC-overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect). On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect), finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis.

Original languageEnglish (US)
Pages (from-to)1007-1017
Number of pages11
JournalNeoplasia (United States)
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Ligands
T-Cell Lymphoma
Transcriptional Activation
Lymphoma
Cell Line
Survival
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Pelullo, M., Quaranta, R., Talora, C., Checquolo, S., Cialfi, S., Felli, M. P. I., ... Bellavia, D. (2014). Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL. Neoplasia (United States), 16(12), 1007-1017. https://doi.org/10.1016/j.neo.2014.10.004

Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL. / Pelullo, Maria; Quaranta, Roberta; Talora, Claudio; Checquolo, Saula; Cialfi, Samantha; Felli, Maria P ia; te Kronnie, Geertruy; Borga, Chiara; Besharat, Zein M ersini; Palermo, Rocco; Di Marcotullio, Lucia; Capobianco, Anthony J; Gulino, Alberto; Screpanti, Isabella; Bellavia, Diana.

In: Neoplasia (United States), Vol. 16, No. 12, 01.12.2014, p. 1007-1017.

Research output: Contribution to journalArticle

Pelullo, M, Quaranta, R, Talora, C, Checquolo, S, Cialfi, S, Felli, MPI, te Kronnie, G, Borga, C, Besharat, ZME, Palermo, R, Di Marcotullio, L, Capobianco, AJ, Gulino, A, Screpanti, I & Bellavia, D 2014, 'Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL', Neoplasia (United States), vol. 16, no. 12, pp. 1007-1017. https://doi.org/10.1016/j.neo.2014.10.004
Pelullo M, Quaranta R, Talora C, Checquolo S, Cialfi S, Felli MPI et al. Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL. Neoplasia (United States). 2014 Dec 1;16(12):1007-1017. https://doi.org/10.1016/j.neo.2014.10.004
Pelullo, Maria ; Quaranta, Roberta ; Talora, Claudio ; Checquolo, Saula ; Cialfi, Samantha ; Felli, Maria P ia ; te Kronnie, Geertruy ; Borga, Chiara ; Besharat, Zein M ersini ; Palermo, Rocco ; Di Marcotullio, Lucia ; Capobianco, Anthony J ; Gulino, Alberto ; Screpanti, Isabella ; Bellavia, Diana. / Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL. In: Neoplasia (United States). 2014 ; Vol. 16, No. 12. pp. 1007-1017.
@article{8a311aabaa6141ccb4f3b154cebb8467,
title = "Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL",
abstract = "Deregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL). Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC-overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect). On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect), finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis.",
author = "Maria Pelullo and Roberta Quaranta and Claudio Talora and Saula Checquolo and Samantha Cialfi and Felli, {Maria P ia} and {te Kronnie}, Geertruy and Chiara Borga and Besharat, {Zein M ersini} and Rocco Palermo and {Di Marcotullio}, Lucia and Capobianco, {Anthony J} and Alberto Gulino and Isabella Screpanti and Diana Bellavia",
year = "2014",
month = "12",
day = "1",
doi = "10.1016/j.neo.2014.10.004",
language = "English (US)",
volume = "16",
pages = "1007--1017",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL

AU - Pelullo, Maria

AU - Quaranta, Roberta

AU - Talora, Claudio

AU - Checquolo, Saula

AU - Cialfi, Samantha

AU - Felli, Maria P ia

AU - te Kronnie, Geertruy

AU - Borga, Chiara

AU - Besharat, Zein M ersini

AU - Palermo, Rocco

AU - Di Marcotullio, Lucia

AU - Capobianco, Anthony J

AU - Gulino, Alberto

AU - Screpanti, Isabella

AU - Bellavia, Diana

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Deregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL). Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC-overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect). On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect), finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis.

AB - Deregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL). Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC-overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect). On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect), finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis.

UR - http://www.scopus.com/inward/record.url?scp=85003322506&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85003322506&partnerID=8YFLogxK

U2 - 10.1016/j.neo.2014.10.004

DO - 10.1016/j.neo.2014.10.004

M3 - Article

C2 - 25499214

AN - SCOPUS:85003322506

VL - 16

SP - 1007

EP - 1017

JO - Neoplasia (United States)

JF - Neoplasia (United States)

SN - 1522-8002

IS - 12

ER -