J 2020

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4(+)CD25(+)FoxP3(+) regulatory T cells activation

LO RE, Oriana; Tommaso MAZZA; Sebastiano GIALLONGO; Paola SANNA; Francesca RAPPA et. al.

Basic information

Original name

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4(+)CD25(+)FoxP3(+) regulatory T cells activation

Authors

LO RE, Oriana; Tommaso MAZZA; Sebastiano GIALLONGO; Paola SANNA; Francesca RAPPA; Tu Vinh Luong LUONG; Giovanni VOLTI; Adéla DVOŘÁKOVÁ; Tania ROSKAMS; Matthias VAN HAELE; Emmanuel TSOCHATZIS and Manlio VINCIGUERRA

Edition

THERANOSTICS, LAKE HAVEN, IVYSPRING INT PUBL, 2020, 1838-7640

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10601 Cell biology

Country of publisher

Australia

Confidentiality degree

is not subject to a state or trade secret

References:

Impact factor

Impact factor: 11.556

RIV identification code

RIV/00216224:14110/20:00116196

Organization unit

Faculty of Medicine

UT WoS

000498874200028

EID Scopus

2-s2.0-85077480426

Keywords in English

hepatocellular carcinoma; histone macroH2A1; adaptive immune system; chemoresistance

Tags

International impact, Reviewed
Changed: 17/3/2021 13:47, Mgr. Tereza Miškechová

Abstract

In the original language

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4(+)/CD25(+)/FoxP3(+) T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance.

Links

LM2015091, research and development project
Name: Národní centrum lékařské genomiky (Acronym: NCLG)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/0951/2019, interní kód MU
Name: Buněčná a molekulární biologie pro Biomedicínské vědy
Investor: Masaryk University, Category A