RNF43 truncations trap CK1 to drive niche-independent
self-renewal in cancer

J 2020

RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer

SPIT, Maureen, Nicola FENDERICO, Ingrid JORDENS, Tomasz Witold RADASZKIEWICZ, Rik G. H. LINDEBOOM et. al.

Základní údaje

Originální název

RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer

Autoři

SPIT, Maureen, Nicola FENDERICO, Ingrid JORDENS, Tomasz Witold RADASZKIEWICZ (616 Polsko, domácí), Rik G. H. LINDEBOOM, Jeroen M. BUGTER, Alba CRISTOBAL, Lars OOTES, Max VAN OSCH, Eline JANSSEN, Kim E. BOONEKAMP, Kateřina HANÁKOVÁ (203 Česká republika, domácí), David POTĚŠIL (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, domácí), Sylvia F. BOJ, Jan Paul MEDEMA, Vítězslav BRYJA (203 Česká republika, domácí), Bon-Kyoung KOO, Michiel VERMEULEN a Madelon M. MAURICE

Vydání

EMBO Journal, Hoboken (USA), Wiley, 2020, 0261-4189

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.598

Kód RIV

RIV/00216224:14310/20:00114578

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.15252/embj.2019103932

UT WoS

000557439600001

Klíčová slova anglicky

cancer mutations; human colon organoids; PORCNinhibitors; RNF43; Wnt signaling

Štítky

CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 11. 2024 20:31, Ing. Martina Blahová

Anotace

V originále

Wnt/beta-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligaseRNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class ofRNF43 truncating cancer mutations that induce beta-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with a ubiquitin-independent suppressor role of theRNF43 cytosolic tail that involves Casein kinase 1 (CK1) binding and phosphorylation. Mechanistically, truncatedRNF43 variants trapCK1 at the plasma membrane, thereby preventing beta-catenin turnover and propelling ligand-independent target gene transcription. Gene editing of human colon stem cells shows thatRNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, theseRNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.

Návaznosti

GX19-28347X, projekt VaV

Název: Molekulární a funkční analýza biologie kasein kinázy 1

Investor: Grantová agentura ČR, Molekulární a funkční analýza biologie kasein kinázy 1

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

SPIT, Maureen, Nicola FENDERICO, Ingrid JORDENS, Tomasz Witold RADASZKIEWICZ, Rik G. H. LINDEBOOM, Jeroen M. BUGTER, Alba CRISTOBAL, Lars OOTES, Max VAN OSCH, Eline JANSSEN, Kim E. BOONEKAMP, Kateřina HANÁKOVÁ, David POTĚŠIL, Zbyněk ZDRÁHAL, Sylvia F. BOJ, Jan Paul MEDEMA, Vítězslav BRYJA, Bon-Kyoung KOO, Michiel VERMEULEN a Madelon M. MAURICE. RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer. EMBO Journal. Hoboken (USA): Wiley, 2020, roč. 39, č. 18, s. 1-15. ISSN 0261-4189. Dostupné z: https://dx.doi.org/10.15252/embj.2019103932.

@article{1710476,
   author = {Spit, Maureen and Fenderico, Nicola and Jordens, Ingrid and Radaszkiewicz, Tomasz Witold and Lindeboom, Rik G. H. and Bugter, Jeroen M. and Cristobal, Alba and Ootes, Lars and van Osch, Max and Janssen, Eline and Boonekamp, Kim E. and Hanáková, Kateřina and Potěšil, David and Zdráhal, Zbyněk and Boj, Sylvia F. and Medema, Jan Paul and Bryja, Vítězslav and Koo, BonandKyoung and Vermeulen, Michiel and Maurice, Madelon M.},
   article_location = {Hoboken (USA)},
   article_number = {18},
   doi = {http://dx.doi.org/10.15252/embj.2019103932},
   keywords = {cancer mutations; human colon organoids; PORCNinhibitors; RNF43; Wnt signaling},
   language = {eng},
   issn = {0261-4189},
   journal = {EMBO Journal},
   title = {RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer},
   url = {https://doi.org/10.15252/embj.2019103932},
   volume = {39},
   year = {2020}
}

TY  - JOUR
ID  - 1710476
AU  - Spit, Maureen - Fenderico, Nicola - Jordens, Ingrid - Radaszkiewicz, Tomasz Witold - Lindeboom, Rik G. H. - Bugter, Jeroen M. - Cristobal, Alba - Ootes, Lars - van Osch, Max - Janssen, Eline - Boonekamp, Kim E. - Hanáková, Kateřina - Potěšil, David - Zdráhal, Zbyněk - Boj, Sylvia F. - Medema, Jan Paul - Bryja, Vítězslav - Koo, Bon-Kyoung - Vermeulen, Michiel - Maurice, Madelon M.
PY  - 2020
TI  - RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer
JF  - EMBO Journal
VL  - 39
IS  - 18
SP  - 1-15
EP  - 1-15
PB  - Wiley
SN  - 02614189
KW  - cancer mutations
KW  - human colon organoids
KW  - PORCNinhibitors
KW  - RNF43
KW  - Wnt signaling
UR  - https://doi.org/10.15252/embj.2019103932
L2  - https://doi.org/10.15252/embj.2019103932
N2  - Wnt/beta-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligaseRNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class ofRNF43 truncating cancer mutations that induce beta-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with a ubiquitin-independent suppressor role of theRNF43 cytosolic tail that involves Casein kinase 1 (CK1) binding and phosphorylation. Mechanistically, truncatedRNF43 variants trapCK1 at the plasma membrane, thereby preventing beta-catenin turnover and propelling ligand-independent target gene transcription. Gene editing of human colon stem cells shows thatRNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, theseRNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.
ER  -

SPIT, Maureen, Nicola FENDERICO, Ingrid JORDENS, Tomasz Witold RADASZKIEWICZ, Rik G. H. LINDEBOOM, Jeroen M. BUGTER, Alba CRISTOBAL, Lars OOTES, Max VAN OSCH, Eline JANSSEN, Kim E. BOONEKAMP, Kateřina HANÁKOVÁ, David POTĚŠIL, Zbyněk ZDRÁHAL, Sylvia F. BOJ, Jan Paul MEDEMA, Vítězslav BRYJA, Bon-Kyoung KOO, Michiel VERMEULEN a Madelon M. MAURICE. RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer. \textit{EMBO Journal}. Hoboken (USA): Wiley, 2020, roč.~39, č.~18, s.~1-15. ISSN~0261-4189. Dostupné z: https://dx.doi.org/10.15252/embj.2019103932.

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