BMP4 enhances anoikis resistance and chemoresistance of breast cancer cells through canonical BMP signaling

Bone morphogenetic proteins (BMPs) regulate cell fate during development and mediate cancer progression. In this study, we investigated the role of BMP4 in proliferation, anoikis resistance, metastatic migration, and drug resistance of breast cancer cells. We utilized breast cancer cell lines and cl...

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Bibliographic Details
Published in:Journal of cell communication and signaling 2022-06, Vol.16 (2), p.191-205
Main Authors: Sharma, Renu, Gogoi, Gayatri, Saikia, Snigdha, Sharma, Amit, Kalita, Deep Jyoti, Sarma, Anupam, Limaye, Anil Mukund, Gaur, Manish Kumar, Bhattacharyya, Jina, Jaganathan, Bithiah Grace
Format: Article
Language:English
Subjects:
Anoikis
anoikis resistance
Apoptosis
Biomedical and Life Sciences
Biomedicine
Bone morphogenetic protein 4
Bone morphogenetic proteins
Breast cancer
cancer stem cells
CD44 antigen
Cell Biology
Cell fate
Cell proliferation
Cell self-renewal
Chemoresistance
Drug resistance
Life Sciences
Metastases
Metastasis
Metastatic migration
Microenvironments
Research Article
Stem cells
TNBC
Tumor cell lines
Tumors
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Summary:Bone morphogenetic proteins (BMPs) regulate cell fate during development and mediate cancer progression. In this study, we investigated the role of BMP4 in proliferation, anoikis resistance, metastatic migration, and drug resistance of breast cancer cells. We utilized breast cancer cell lines and clinical samples representing different subtypes to understand the functional effect of BMP4 on breast cancer. The BMP pathway was inhibited with the small molecule inhibitor LDN193189 hydrochloride (LDN). BMP4 signaling enhanced the expression of stem cell genes CD44, ALDH1A3, anti-apoptotic gene BCL2 and promoted anoikis resistance in MDA-MB-231 breast cancer cells. BMP4 enhanced self-renewal and chemoresistance in MDA-MB-231 by upregulating Notch signaling while LDN treatment abrogated anoikis resistance and proliferation of anoikis resistant breast cancer cells in the osteogenic microenvironment. Conversely, BMP4 downregulated proliferation, colony-forming ability, and suppressed anoikis resistance in MCF7 and SkBR3 cells, while LDN treatment promoted tumor spheroid formation and growth. These findings indicate that BMP4 has a context-dependent role in breast cancer. Further, our data with MDA-MB-231 cells representing triple-negative breast cancer suggest that BMP inhibition might impair its metastatic spread and colonization.
ISSN:1873-9601
1873-961X
DOI:10.1007/s12079-021-00649-9