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

• Published in: Journal of cell communication and signaling Vol. 16; no. 2; pp. 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: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2022; John Wiley & Sons, Inc
• 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; chemoresistance; Metastatic migration; cancer stem cells; TNBC; anoikis resistance
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-021-00649-9

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.