Lactate dehydrogenase A regulates autophagy and tamoxifen resistance in breast cancer
Copyright © 2019 Elsevier B.V. All rights reserved..
Estrogen receptor (ER) antagonist, tamoxifen has been universally used for the treatment of the ER-positive breast cancer; however, the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer. So, there is an immediate requirement for the search of a novel therapeutic target for treatment of this cancer. Acquired tamoxifen-resistant breast cancer cell lines MCF-7 (MCF-7/TAM-R) and T47D (T47D/TAM-R) showed higher apoptotic resistance accompanied by induction of pro-survival autophagy compared to their parental cells. Besides, tamoxifen resistance was associated with reduced production of ATP and with overexpression of glycolytic pathways, leading to induced autophagy to meet the energy demand. Further, our study revealed that LDHA; one of the key molecules of glycolysis in association with Beclin-1 induced pro-survival autophagy in tamoxifen-resistant breast cancer. Mechanistically, pharmacological and genetic inhibition of LDHA reduced the pro-survival autophagy, with the restoration of apoptosis and reverting back the EMT like phenomena noticed in tamoxifen-resistant breast cancer. In total, targeting LDHA opened a novel strategy to interrupt autophagy and tamoxifen resistance in breast cancer.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1866 |
|---|---|
| Enthalten in: |
Biochimica et biophysica acta. Molecular cell research - 1866(2019), 6 vom: 05. Juni, Seite 1004-1018 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Das, Chandan Kanta [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.10.2019 Date Revised 22.10.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbamcr.2019.03.004 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM295015330 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM295015330 | ||
| 003 | DE-627 | ||
| 005 | 20231225082735.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbamcr.2019.03.004 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0983.xml |
| 035 | |a (DE-627)NLM295015330 | ||
| 035 | |a (NLM)30878502 | ||
| 035 | |a (PII)S0167-4889(19)30027-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Das, Chandan Kanta |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lactate dehydrogenase A regulates autophagy and tamoxifen resistance in breast cancer |
| 264 | 1 | |c 2019 | |
| 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 21.10.2019 | ||
| 500 | |a Date Revised 22.10.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
| 520 | |a Estrogen receptor (ER) antagonist, tamoxifen has been universally used for the treatment of the ER-positive breast cancer; however, the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer. So, there is an immediate requirement for the search of a novel therapeutic target for treatment of this cancer. Acquired tamoxifen-resistant breast cancer cell lines MCF-7 (MCF-7/TAM-R) and T47D (T47D/TAM-R) showed higher apoptotic resistance accompanied by induction of pro-survival autophagy compared to their parental cells. Besides, tamoxifen resistance was associated with reduced production of ATP and with overexpression of glycolytic pathways, leading to induced autophagy to meet the energy demand. Further, our study revealed that LDHA; one of the key molecules of glycolysis in association with Beclin-1 induced pro-survival autophagy in tamoxifen-resistant breast cancer. Mechanistically, pharmacological and genetic inhibition of LDHA reduced the pro-survival autophagy, with the restoration of apoptosis and reverting back the EMT like phenomena noticed in tamoxifen-resistant breast cancer. In total, targeting LDHA opened a novel strategy to interrupt autophagy and tamoxifen resistance in breast cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a ER-positive breast cancer | |
| 650 | 4 | |a Glycolysis | |
| 650 | 4 | |a LDHA | |
| 650 | 4 | |a Tamoxifen resistance | |
| 650 | 7 | |a BECN1 protein, human |2 NLM | |
| 650 | 7 | |a Beclin-1 |2 NLM | |
| 650 | 7 | |a Tamoxifen |2 NLM | |
| 650 | 7 | |a 094ZI81Y45 |2 NLM | |
| 650 | 7 | |a L-Lactate Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.1.1.27 |2 NLM | |
| 650 | 7 | |a LDHA protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.27 |2 NLM | |
| 650 | 7 | |a Proteasome Endopeptidase Complex |2 NLM | |
| 650 | 7 | |a EC 3.4.25.1 |2 NLM | |
| 700 | 1 | |a Parekh, Aditya |e verfasserin |4 aut | |
| 700 | 1 | |a Parida, Pratap Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Bhutia, Sujit Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Mandal, Mahitosh |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochimica et biophysica acta. Molecular cell research |d 2017 |g 1866(2019), 6 vom: 05. Juni, Seite 1004-1018 |w (DE-627)NLM264216326 |x 1879-2596 |7 nnns |
| 773 | 1 | 8 | |g volume:1866 |g year:2019 |g number:6 |g day:05 |g month:06 |g pages:1004-1018 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbamcr.2019.03.004 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 1866 |j 2019 |e 6 |b 05 |c 06 |h 1004-1018 | ||