Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis
Summary: Oncogenic mutations in the EGFR gene account for 15–20% of lung adenocarcinoma (LUAD) cases. However, the mechanism for EGFR driven tumor development and growth is not fully understood. Here, using an mRNA expression profiling-based approach we identified betacellulin (BTC) as one the gene...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222004813 |
| _version_ | 1818552035352510464 |
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| author | Suresh Chava Suresh Bugide Xuchen Zhang Romi Gupta Narendra Wajapeyee |
| author_facet | Suresh Chava Suresh Bugide Xuchen Zhang Romi Gupta Narendra Wajapeyee |
| author_sort | Suresh Chava |
| collection | DOAJ |
| description | Summary: Oncogenic mutations in the EGFR gene account for 15–20% of lung adenocarcinoma (LUAD) cases. However, the mechanism for EGFR driven tumor development and growth is not fully understood. Here, using an mRNA expression profiling-based approach we identified betacellulin (BTC) as one the gene upregulated by oncogenic EGFR in an MAP kinase-dependent manner. BTC protein expression was markedly increased in LUAD patient samples compared to normal lung tissue, with higher expression in EGFR-mutant LUAD. BTC was sufficient to transform immortalized mouse cells, initiate tumor development in mice, and promote the survival of immortalized human lung epithelial cells. Conversely, knockdown of BTC inhibited the growth of EGFR-mutant human LUAD cells in culture and their tumor-forming ability in mice. Mechanistically, BTC knockdown resulted in attenuated EGFR signaling and apoptosis induction. Collectively, these results demonstrate a key role of BTC in EGFR-mutant LUAD, with potential therapeutic implications in LUAD and other EGFR-mutant cancers. |
| first_indexed | 2024-12-12T09:07:50Z |
| format | Article |
| id | doaj.art-21e6333ab6b5475c897030ecaebc4be2 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T09:07:50Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-21e6333ab6b5475c897030ecaebc4be22022-12-22T00:29:37ZengElsevieriScience2589-00422022-05-01255104211Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosisSuresh Chava0Suresh Bugide1Xuchen Zhang2Romi Gupta3Narendra Wajapeyee4Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Pathology, Yale University, New Haven, CT 06510, USADepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Corresponding authorDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Corresponding authorSummary: Oncogenic mutations in the EGFR gene account for 15–20% of lung adenocarcinoma (LUAD) cases. However, the mechanism for EGFR driven tumor development and growth is not fully understood. Here, using an mRNA expression profiling-based approach we identified betacellulin (BTC) as one the gene upregulated by oncogenic EGFR in an MAP kinase-dependent manner. BTC protein expression was markedly increased in LUAD patient samples compared to normal lung tissue, with higher expression in EGFR-mutant LUAD. BTC was sufficient to transform immortalized mouse cells, initiate tumor development in mice, and promote the survival of immortalized human lung epithelial cells. Conversely, knockdown of BTC inhibited the growth of EGFR-mutant human LUAD cells in culture and their tumor-forming ability in mice. Mechanistically, BTC knockdown resulted in attenuated EGFR signaling and apoptosis induction. Collectively, these results demonstrate a key role of BTC in EGFR-mutant LUAD, with potential therapeutic implications in LUAD and other EGFR-mutant cancers.http://www.sciencedirect.com/science/article/pii/S2589004222004813Cell biologyCancerTranscriptomics |
| spellingShingle | Suresh Chava Suresh Bugide Xuchen Zhang Romi Gupta Narendra Wajapeyee Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis iScience Cell biology Cancer Transcriptomics |
| title | Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis |
| title_full | Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis |
| title_fullStr | Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis |
| title_full_unstemmed | Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis |
| title_short | Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis |
| title_sort | betacellulin promotes tumor development and egfr mutant lung cancer growth by stimulating the egfr pathway and suppressing apoptosis |
| topic | Cell biology Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222004813 |
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