TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling
Transforming growth factor (TGF)-β and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 2024
|
| In: |
International journal of experimental pathology
Year: 2024, Volume: 105, Issue: 2, Pages: 64-74 |
| ISSN: | 1365-2613 |
| DOI: | 10.1111/iep.12501 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/iep.12501 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/iep.12501 
|
| Author Notes: | Fatma El Zahraa Ammar Mohamed, Bedair Dewidar, Tao Lin, Matthias P. Ebert, Steven Dooley, Nadja M. Meindl-Beinker, Seddik Hammad |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1891787365 | ||
| 003 | DE-627 | ||
| 005 | 20241205143308.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240620s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/iep.12501 |2 doi | |
| 035 | |a (DE-627)1891787365 | ||
| 035 | |a (DE-599)KXP1891787365 | ||
| 035 | |a (OCoLC)1475300136 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Mohamed, Fatma El Zahraa |d 1976- |e VerfasserIn |0 (DE-588)1161550070 |0 (DE-627)1024830977 |0 (DE-576)506717860 |4 aut | |
| 245 | 1 | 0 | |a TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling |c Fatma El Zahraa Ammar Mohamed, Bedair Dewidar, Tao Lin, Matthias P. Ebert, Steven Dooley, Nadja M. Meindl-Beinker, Seddik Hammad |
| 246 | 3 | 3 | |a TGF beta R1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling |
| 264 | 1 | |c April 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Veröffentlicht: 08 February 2024 | ||
| 500 | |a Gesehen am 20.06.2024 | ||
| 520 | |a Transforming growth factor (TGF)-β and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the possibility of such interaction. A human HCC tissue array (n = 20 vs. four control samples), human HCC samples (n = 10) and steatohepatitis-driven murine HCC samples (control, NASH and HCC; n = 6/group) were immunostained for TGFβR1, pSMAD2, TRAF6, IRAK1 and PCNA. The results were confirmed by immunoblotting. Effects of constant activation of the SMAD pathway by constitutive expression of ALK5 or knockdown of mediators of TLR signalling, IRAK1 and MyD88, on HCC proliferation, were investigated in the HCC cell line (HUH-7) after treatment with TGFβ1 cytokine or TGFβR1 kinase inhibitor (LY2157299) using PCNA and MTS assay. TGFβR1 expression is decreased in human and murine HCC and associated with downregulated pSMAD2, but increased IRAK1, TRAF6 and PCNA staining. TGFβR1 kinase inhibition abolished the cytostatic effects of TGFβ1 and led to the induction of IRAK1, pIRAK1 and elevated mRNA levels of TLR-9. Overexpression of ALK5 and knockdown of MyD88 or IRAK1 augmented the cytostatic effects of TGFβ1 on HUH-7. In another epithelial HCC cell line, that is, HepG2, TGFβR1 kinase inhibitor similarly elevated cellular proliferation. There is a balance between the canonical SMAD-driven tumour-suppressing arm and the non-canonical tumour-promoting arm of TGFβ signalling. Disruption of this balance, by inhibition of the canonical pathway, induces HCC proliferation through TLR signalling. | ||
| 650 | 4 | |a HCC | |
| 650 | 4 | |a TGFβ signalling | |
| 650 | 4 | |a TGFβR1 | |
| 650 | 4 | |a toll-like receptors | |
| 650 | 4 | |a TRAF6 | |
| 700 | 1 | |a Dewidar, Bedair |d 1984- |e VerfasserIn |0 (DE-588)1161117652 |0 (DE-627)1024530922 |0 (DE-576)50636707X |4 aut | |
| 700 | 1 | |a Lin, Tao |d 1988- |e VerfasserIn |0 (DE-588)1206437383 |0 (DE-627)1692463462 |4 aut | |
| 700 | 1 | |a Ebert, Matthias |d 1968- |e VerfasserIn |0 (DE-588)1030133522 |0 (DE-627)734827083 |0 (DE-576)377938432 |4 aut | |
| 700 | 1 | |a Dooley, Steven |d 1960- |e VerfasserIn |0 (DE-588)1028589190 |0 (DE-627)73128951X |0 (DE-576)376074116 |4 aut | |
| 700 | 1 | |a Meindl-Beinker, Nadja M. |d 1975- |e VerfasserIn |0 (DE-588)124950159 |0 (DE-627)368960056 |0 (DE-576)294584757 |4 aut | |
| 700 | 1 | |a Hammad, Seddik |d 1978- |e VerfasserIn |0 (DE-588)1026472296 |0 (DE-627)72676891X |0 (DE-576)371820863 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of experimental pathology |d Oxford [u.a.] : Wiley-Blackwell, 1990 |g 105(2024), 2 vom: Apr., Seite 64-74 |h Online-Ressource |w (DE-627)320482758 |w (DE-600)2010007-3 |w (DE-576)091143071 |x 1365-2613 |7 nnas |a TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling |
| 773 | 1 | 8 | |g volume:105 |g year:2024 |g number:2 |g month:04 |g pages:64-74 |g extent:11 |a TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling |
| 856 | 4 | 0 | |u https://doi.org/10.1111/iep.12501 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1111/iep.12501 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240620 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 1026472296 |a Hammad, Seddik |m 1026472296:Hammad, Seddik |d 60000 |d 61100 |e 60000PH1026472296 |e 61100PH1026472296 |k 0/60000/ |k 1/60000/61100/ |p 7 |y j | ||
| 998 | |g 124950159 |a Meindl-Beinker, Nadja M. |m 124950159:Meindl-Beinker, Nadja M. |d 60000 |d 61100 |e 60000PM124950159 |e 61100PM124950159 |k 0/60000/ |k 1/60000/61100/ |p 6 | ||
| 998 | |g 1028589190 |a Dooley, Steven |m 1028589190:Dooley, Steven |d 60000 |d 61100 |e 60000PD1028589190 |e 61100PD1028589190 |k 0/60000/ |k 1/60000/61100/ |p 5 | ||
| 998 | |g 1030133522 |a Ebert, Matthias |m 1030133522:Ebert, Matthias |d 60000 |d 61100 |e 60000PE1030133522 |e 61100PE1030133522 |k 0/60000/ |k 1/60000/61100/ |p 4 | ||
| 998 | |g 1206437383 |a Lin, Tao |m 1206437383:Lin, Tao |d 60000 |d 61100 |e 60000PL1206437383 |e 61100PL1206437383 |k 0/60000/ |k 1/60000/61100/ |p 3 | ||
| 998 | |g 1161117652 |a Dewidar, Bedair |m 1161117652:Dewidar, Bedair |p 2 | ||
| 998 | |g 1161550070 |a Mohamed, Fatma El Zahraa |m 1161550070:Mohamed, Fatma El Zahraa |p 1 |x j | ||
| 999 | |a KXP-PPN1891787365 |e 4540443909 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"April 2024"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"display":"Mohamed, Fatma El Zahraa","family":"Mohamed","given":"Fatma El Zahraa","role":"aut"},{"family":"Dewidar","given":"Bedair","display":"Dewidar, Bedair","role":"aut"},{"family":"Lin","given":"Tao","display":"Lin, Tao","role":"aut"},{"given":"Matthias","family":"Ebert","display":"Ebert, Matthias","role":"aut"},{"display":"Dooley, Steven","family":"Dooley","given":"Steven","role":"aut"},{"family":"Meindl-Beinker","given":"Nadja M.","display":"Meindl-Beinker, Nadja M.","role":"aut"},{"family":"Hammad","given":"Seddik","display":"Hammad, Seddik","role":"aut"}],"title":[{"title_sort":"TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling","title":"TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling"}],"note":["Veröffentlicht: 08 February 2024","Gesehen am 20.06.2024"],"relHost":[{"note":["Gesehen am 05.12.11"],"title":[{"title":"International journal of experimental pathology","title_sort":"International journal of experimental pathology"}],"pubHistory":["71.1990 -"],"origin":[{"publisherPlace":"Oxford [u.a.] ; Oxford [u.a.] ; Oxford [u.a.]","dateIssuedDisp":"1990-","publisher":"Wiley-Blackwell ; Blackwell Science ; Blackwell","dateIssuedKey":"1990"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"physDesc":[{"extent":"Online-Ressource"}],"disp":"TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signallingInternational journal of experimental pathology","part":{"pages":"64-74","volume":"105","extent":"11","issue":"2","year":"2024","text":"105(2024), 2 vom: Apr., Seite 64-74"},"titleAlt":[{"title":"Journal of experimental pathology"}],"language":["eng"],"recId":"320482758","id":{"zdb":["2010007-3"],"issn":["1365-2613"],"doi":["10.1111/(ISSN)1365-2613"],"eki":["320482758"]}}],"name":{"displayForm":["Fatma El Zahraa Ammar Mohamed, Bedair Dewidar, Tao Lin, Matthias P. Ebert, Steven Dooley, Nadja M. Meindl-Beinker, Seddik Hammad"]},"recId":"1891787365","id":{"doi":["10.1111/iep.12501"],"eki":["1891787365"]},"language":["eng"],"physDesc":[{"noteIll":"Illustrationen","extent":"11 S."}],"titleAlt":[{"title":"TGF beta R1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling"}]} | ||
| SRT | |a MOHAMEDFATTGFR1INHIB2024 | ||