Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer
Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J.
The American Association for Cancer Research (AACR)
Published 2018
The American Association for Cancer Research (AACR)
Published 2018
| Publication Date: |
2018-05-02
|
|---|---|
| Publisher: |
The American Association for Cancer Research (AACR)
|
| Print ISSN: |
1078-0432
|
| Electronic ISSN: |
1557-3265
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398915137568768 |
|---|---|
| autor | Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. |
| beschreibung | Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α21 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α21-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α21-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α21-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α21-mediated chemoresistance were examined. Results: Different proportions of α21 + cells were identified in SCLC cell lines and PDX models. α21 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α21 + cells instead of CD133 + cells in PDXs, and an increased proportion of α21 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α21-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α21 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α21-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR . |
| citation_standardnr | 6248674 |
| datenlieferant | ipn_articles |
| feed_id | 9363 |
| feed_publisher | The American Association for Cancer Research (AACR) |
| feed_publisher_url | http://www.aacr.org/ |
| insertion_date | 2018-05-02 |
| journaleissn | 1557-3265 |
| journalissn | 1078-0432 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association for Cancer Research (AACR) |
| quelle | Clinical Cancer Research |
| relation | http://clincancerres.aacrjournals.org/cgi/content/short/24/9/2148?rss=1 |
| search_space | articles |
| shingle_author_1 | Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. |
| shingle_author_2 | Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. |
| shingle_author_3 | Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. |
| shingle_author_4 | Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. |
| shingle_catch_all_1 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α21 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α21-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α21-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α21-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α21-mediated chemoresistance were examined. Results: Different proportions of α21 + cells were identified in SCLC cell lines and PDX models. α21 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α21 + cells instead of CD133 + cells in PDXs, and an increased proportion of α21 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α21-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α21 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α21-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR . Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_2 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α21 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α21-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α21-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α21-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α21-mediated chemoresistance were examined. Results: Different proportions of α21 + cells were identified in SCLC cell lines and PDX models. α21 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α21 + cells instead of CD133 + cells in PDXs, and an increased proportion of α21 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α21-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α21 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α21-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR . Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_3 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α21 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α21-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α21-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α21-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α21-mediated chemoresistance were examined. Results: Different proportions of α21 + cells were identified in SCLC cell lines and PDX models. α21 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α21 + cells instead of CD133 + cells in PDXs, and an increased proportion of α21 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α21-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α21 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α21-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR . Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_4 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α21 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α21-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α21-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α21-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α21-mediated chemoresistance were examined. Results: Different proportions of α21 + cells were identified in SCLC cell lines and PDX models. α21 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α21 + cells instead of CD133 + cells in PDXs, and an increased proportion of α21 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α21-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α21 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α21-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR . Yu, J., Wang, S., Zhao, W., Duan, J., Wang, Z., Chen, H., Tian, Y., Wang, D., Zhao, J., An, T., Bai, H., Wu, M., Wang, J. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_title_1 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| shingle_title_2 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| shingle_title_3 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| shingle_title_4 | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| timestamp | 2025-06-30T23:34:39.542Z |
| titel | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| titel_suche | Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel {alpha}2{delta}1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer |
| topic | WW-YZ |
| uid | ipn_articles_6248674 |