The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer

Soyeon Bang; Junhong Li; Meiqin Zhang; Renjie Cui; Xingwen Wu; Zhaochen Xin; Duan Ma; Jin Zhang; Hongwei Zhang

doi:10.2147/CMAR.S256490

The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer

Cancer Manag Res. 2020 Jul 27:12:6373-6383. doi: 10.2147/CMAR.S256490. eCollection 2020.

Authors

Soyeon Bang¹, Junhong Li², Meiqin Zhang³, Renjie Cui³, Xingwen Wu⁴, Zhaochen Xin¹, Duan Ma^{3

5}, Jin Zhang³, Hongwei Zhang¹

Affiliations

¹ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
² Department of Urology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, People's Republic of China.
³ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
⁴ Department of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
⁵ Children's Hospital, Fudan University, Shanghai, People's Republic of China.

Abstract

Background: Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive.

Methods: We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan-Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting.

Results: Using publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial-mesenchymal transition (EMT).

Conclusion: Our results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.

Keywords: EMT; Krüppel-like factor 16; breast cancer; metastasis; proliferation.