Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer
BACKGROUND: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process.
METHODS: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation. The functional roles and downstream signalling of PDK4 were explored. Its association with clinical outcome of ovarian cancer was analysed.
RESULTS: We demonstrated enhanced CSC characteristics of tumour cells derived from ovarian cancer ascites, concomitant with ALDH and CD44 subset enrichment and high PDK4 expression, compared to primary tumours. We further showed tumourspheres/ALDH+CD44+ subsets from ascites-derived tumour cells/cell lines with CSC properties and enhanced glycolysis. Clinically, PDK4 expression was correlated with aggressive features. Notably, blockade of PDK4 in tumourspheres/ALDH+CD44+ subsets led to inhibition of CSC characteristics, glycolysis and activation of STAT3/AKT/NF-κB/IL-8 (signal transducer and activator of transcription 3/protein kinases B/nuclear factor-κB/interleukin-8) signalling. Conversely, overexpression of PDK4 in ALDH-CD44- subsets exerted the opposite effects.
CONCLUSION: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastatic and metabolic switch properties via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling, suggesting PDK4 as a viable therapeutic molecular target for ovarian cancer management.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:123 |
|---|---|
| Enthalten in: |
British journal of cancer - 123(2020), 2 vom: 11. Juli, Seite 275-287 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jiang, Yu-Xin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 19.02.2021 Date Revised 11.05.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41416-020-0865-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM309732182 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM309732182 | ||
| 003 | DE-627 | ||
| 005 | 20231225134549.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41416-020-0865-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1032.xml |
| 035 | |a (DE-627)NLM309732182 | ||
| 035 | |a (NLM)32390009 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jiang, Yu-Xin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.02.2021 | ||
| 500 | |a Date Revised 11.05.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process | ||
| 520 | |a METHODS: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation. The functional roles and downstream signalling of PDK4 were explored. Its association with clinical outcome of ovarian cancer was analysed | ||
| 520 | |a RESULTS: We demonstrated enhanced CSC characteristics of tumour cells derived from ovarian cancer ascites, concomitant with ALDH and CD44 subset enrichment and high PDK4 expression, compared to primary tumours. We further showed tumourspheres/ALDH+CD44+ subsets from ascites-derived tumour cells/cell lines with CSC properties and enhanced glycolysis. Clinically, PDK4 expression was correlated with aggressive features. Notably, blockade of PDK4 in tumourspheres/ALDH+CD44+ subsets led to inhibition of CSC characteristics, glycolysis and activation of STAT3/AKT/NF-κB/IL-8 (signal transducer and activator of transcription 3/protein kinases B/nuclear factor-κB/interleukin-8) signalling. Conversely, overexpression of PDK4 in ALDH-CD44- subsets exerted the opposite effects | ||
| 520 | |a CONCLUSION: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastatic and metabolic switch properties via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling, suggesting PDK4 as a viable therapeutic molecular target for ovarian cancer management | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a CD44 protein, human |2 NLM | |
| 650 | 7 | |a Hyaluronan Receptors |2 NLM | |
| 650 | 7 | |a Interleukin-8 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a PDK4 protein, human |2 NLM | |
| 650 | 7 | |a Pyruvate Dehydrogenase Acetyl-Transferring Kinase |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-8A |2 NLM | |
| 650 | 7 | |a STAT3 Transcription Factor |2 NLM | |
| 650 | 7 | |a STAT3 protein, human |2 NLM | |
| 650 | 7 | |a Aldehyde Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.2.1.3 |2 NLM | |
| 650 | 7 | |a Oncogene Protein v-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Siu, Michelle Kwan-Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing-Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Xue-Tang |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Thomas Ho-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, David Wai |e verfasserin |4 aut | |
| 700 | 1 | |a Cheung, Annie Nga-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Ngan, Hextan Yuen-Sheung |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Karen Kar-Loen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of cancer |d 1947 |g 123(2020), 2 vom: 11. Juli, Seite 275-287 |w (DE-627)NLM000027537 |x 1532-1827 |7 nnns |
| 773 | 1 | 8 | |g volume:123 |g year:2020 |g number:2 |g day:11 |g month:07 |g pages:275-287 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41416-020-0865-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 123 |j 2020 |e 2 |b 11 |c 07 |h 275-287 | ||