BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia
Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022024781 |
| _version_ | 1811325773286473728 |
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| author | Hongmei Li Can Zhang Qiong Zhang Jiezhi Jia Xiaojiao Wang |
| author_facet | Hongmei Li Can Zhang Qiong Zhang Jiezhi Jia Xiaojiao Wang |
| author_sort | Hongmei Li |
| collection | DOAJ |
| description | Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells in vitro. In the present study, we found that BNIP3 expression was elevated and enhanced the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. The upregulation of BNIP3 was important for the autophagic activation, while inhibition of autophagy with siRNA targeting Atg5 and Atg7 impaired the hypoxia-induced cell migration and proliferation. Additionally, blocking ERK1/2 mitogen-activated protein kinase (MAPK) signaling with PD98058 significantly down-regulated BNIP3 expression, autophagic activation, as well as the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. Collectively, our results here uncover a hitherto unknown hypoxia-BNIP3-autophagy axis in modulating the migration and proliferation and provide a potential intriguing drug target for the therapy of PDAC. |
| first_indexed | 2024-04-13T14:39:39Z |
| format | Article |
| id | doaj.art-7f09baba12c24569a1cd6f99b8987f83 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-13T14:39:39Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-7f09baba12c24569a1cd6f99b8987f832022-12-22T02:42:56ZengElsevierHeliyon2405-84402022-10-01810e11190BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxiaHongmei Li0Can Zhang1Qiong Zhang2Jiezhi Jia3Xiaojiao Wang4Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, ChinaDepartment of Plastic Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, ChinaInstitute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, ChinaInstitute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, ChinaDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Corresponding author.Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells in vitro. In the present study, we found that BNIP3 expression was elevated and enhanced the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. The upregulation of BNIP3 was important for the autophagic activation, while inhibition of autophagy with siRNA targeting Atg5 and Atg7 impaired the hypoxia-induced cell migration and proliferation. Additionally, blocking ERK1/2 mitogen-activated protein kinase (MAPK) signaling with PD98058 significantly down-regulated BNIP3 expression, autophagic activation, as well as the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. Collectively, our results here uncover a hitherto unknown hypoxia-BNIP3-autophagy axis in modulating the migration and proliferation and provide a potential intriguing drug target for the therapy of PDAC.http://www.sciencedirect.com/science/article/pii/S2405844022024781BNIP3AutophagyERK1/2Pancreatic ductal adenocarcinomaHypoxia |
| spellingShingle | Hongmei Li Can Zhang Qiong Zhang Jiezhi Jia Xiaojiao Wang BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia Heliyon BNIP3 Autophagy ERK1/2 Pancreatic ductal adenocarcinoma Hypoxia |
| title | BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| title_full | BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| title_fullStr | BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| title_full_unstemmed | BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| title_short | BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| title_sort | bnip3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia |
| topic | BNIP3 Autophagy ERK1/2 Pancreatic ductal adenocarcinoma Hypoxia |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022024781 |
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