MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression. (7th June 2022)

• Record Type: Journal Article
• Authors: Li, Wenjie; Qian, Cheng; Ma, Fei; Liu, Meng; Sun, Xiaojun; Liu, Xu; Liu, Chunxiao; Chen, Zhenghua; Ma, Weichang; Liu, Jian; Xu, Haiqian; Yang, Zhenlin
• Other Names: Papaccio Gianpaolo Academic Editor.
• Is Part Of: Stem cells international. Volume 2022(2022)
• Publication Date: 2022-06-07
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2022/8540535
• Languages: English
• ISSNs: 1687-966X

Abstract

Abstract : Adipose-derived stem cells (ASCs) improve the self-renewal and survival of fat grafts in breast reconstruction after oncology surgery. However, ASCs have also been found to enhance breast cancer growth, and its role in tumor proliferation remains largely elusive. Here, we explored a novel mechanism that mediates hTERT reactivation during ASC-induced tumor growth in breast cancer cells. In this study, we found the proliferative ability of breast cancer cells markedly increased with ASC coculture. To explore the molecular mechanism, we treated cells with anibody/inhibitor and found that the activation of MEK-ERK pathway was triggered in breast cancer cells by SCF secreted from ASCs, leading to the nuclear recruitment of CBP. As a coactivator of hTERT, CBP subsequently coordinated with RFPL-3 upregulated hTERT transcription and telomerase activity. The inhibition of CBP and RFPL-3 abrogated the activation of hTERT transcription and the promotion of proliferation in breast cancer cells with cocultured ASCs in vitro and in vivo. Collectively, our study findings indicated that CBP coordination with RFPL-3 promotes ASC-induced breast cancer cell proliferation by anchoring to the hTERT promoter and upregulating telomerase activity, which is activated by the MAPK/ERK pathway.