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- Title
Cholesterol Synthesis Is Important for Breast Cancer Cell Tumor Sphere Formation and Invasion.
- Authors
Kim, Hee Yeon; Bae, Sung Jin; Choi, Ji-Woong; Han, Suji; Bae, Seung-Hyun; Cheong, Jae-Ho; Jang, Hyonchol
- Abstract
Breast cancer has a high risk of recurrence and distant metastasis after remission. Controlling distant metastasis is important for reducing breast cancer mortality, but accomplishing this goal remains elusive. In this study, we investigated the molecular pathways underlying metastasis using cells that mimic the breast cancer distant metastasis process. HCC1143 breast cancer cells were cultured under two-dimensional (2D)-adherent, tumor sphere (TS), and reattached (ReA) culture conditions to mimic primary tumors, circulating tumor cells, and metastasized tumors, respectively. ReA cells demonstrated increased TS formation and enhanced invasion capacity compared to the original 2D-cultured parental cells. In addition, ReA cells had a higher frequency of ESA+CD44+CD24− population, which represents a stem-cell-like cell population. RNA sequencing identified the cholesterol synthesis pathway as one of the most significantly increased pathways in TS and ReA cells compared to parental cells, which was verified by measuring intracellular cholesterol levels. Furthermore, the pharmacological inhibition of the cholesterol synthesis pathway decreased the ability of cancer cells to form TSs and invade. Our results suggest that the cholesterol synthesis pathway plays an important role in the distant metastasis of breast cancer cells by augmenting TS formation and invasion capacity.
- Subjects
METASTATIC breast cancer; BREAST cancer; CANCER cell culture; CELL tumors; CANCER cells; HYDROXYCHOLESTEROLS
- Publication
Biomedicines, 2022, Vol 10, Issue 8, pN.PAG
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines10081908