The role of BMP8A in breast cancer and its involvement in bone metastasis

Sui, Laijian 2022. The role of BMP8A in breast cancer and its involvement in bone metastasis. MD Thesis, Cardiff University. Item availability restricted.

Preview	PDF - Accepted Post-Print Version Download (9MB) | Preview
	PDF (Cardiff University Electronic Publication Form) - Supplemental Material Restricted to Repository staff only Download (140kB)

Abstract

Emerging evidence showed a putative oncogenic role played by bone morphogenetic protein 8A (BMP8A) in breast cancer. The present study aims to dissect the role played by BMP8A in breast cancer. Initial analyses showed that BMP8A was increased in the tissues of primary breast cancer at both mRNA and protein levels. The elevated expression was associated with poorer survival of patients with luminal B tumours but tends to be a feasible marker for overall survival of patients with HER2 positive tumours suggesting a subtype specific involvement. BMP8A promoted invasion of luminal B cancer cells by upregulating MMPs and promoting EMT in which both Smad dependent and independent signalling are involved. Similarly, BMP8A also enhanced the invasiveness of HER2 positive breast cancer cells by promoting MMPs and EMT. However, BMP8A exhibited both inhibitory and promotive effects on proliferation of HCC1419 and SKBR3 cells, respectively. These altered cell behaviours may be coordinated by BMP8A through orchestrated signalling comprising Smad1/5/8, MAPK (ERK) and AKT pathways in HER2 positive tumours. Increased cell invasion together with upregulated MMPs and EMT by BMP8A were also seen in TNBC (triple negative breast cancer) cells, in which elevated expression of EGFR and activation of Smad3 were observed. There was positive correlation between BMP8A and osteoblastic/osteolytic markers revealed in primary tumours of breast cancer. Together with the observed activation of RANKL/P38 signalling in the BMP8A overexpression MDA-MB-231 cells, it collectively suggests that BMP8A may be actively involved in the bone metastasis of breast cancer. In conclusion, BMP8A is upregulated in breast cancer which presents subtype specific correlation with patients’ survival. It promotes invasion of breast cancer through a promotion of MMPs and EMT in which both Smad dependent and independent signalling are involved. Further study will shed light on its therapeutic potential in the personalised disease management of different subtype breast cancer.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	3 November 2022
Last Modified:	03 Nov 2023 02:30
URI:	https://orca.cardiff.ac.uk/id/eprint/153968

Actions (repository staff only)

Edit Item