The upregulation of SIK3 expression in breast cancer promotes breast cancer cell proliferation and metastasis under high salt treatment. The Oncomine and UALCAN showed that mRNA and protein expression of SIK3 were significantly higher in breast cancer tissue compared with normal tissue (Fig. 1 A–E). Elevated expression levels of SIK3 have also been

found in breast cancer cell lines compared to non-malignant cell lines. High expression of salt-inducible kinases 3 (SIK3) kinase promotes mTOR/Akt signalling pathways, which leads to the progression of breast cancer. Emodin and Berberine significantly inhibit SIK3 activity,

thereby exert an anti-cancer effect in breast cancer cells. Emodin and Berberine attenuates aerobic glycolysis and cell growth as well as induce cell death by suppressing the SIK3/mTOR/Akt signalling pathways in breast cancer cells.

The proposed mechanism of emodin in combined with berberine exert anti cancer effects in breast cancer cells via attenuation of SIK3-induced mTOR/Akt signalling pathway. In breast cancer cells, SIK3 physically interacts with TSC2 and negatively regulates its activity,

leading to augmented mTOR signalling, which in turn stimulates aerobic glycolysis and cell proliferation. In addition, SIK3 interact with Akt and potentiates its activity, thereby promoting cell survival and suppressing apoptotic cell death. Upon treatment of cells with

EMO and BBR), treatment inhibits SIK3 activity as well as disturbs the association between SIK3 and TSC2/Akt, resulting in the stimulation of breast cancer cell death by inhibiting cell survival and proliferation.

Reference

Ponnusamy, L., Kothandan, G., & Manoharan, R. (2020). Berberine and Emodin abrogates breast cancer growth and facilitates apoptosis through inactivation of SIK3-induced mTOR and Akt signaling pathway. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1866(11), 165897. https://doi.org/https://doi.org/10.1016/j.bbadis.2020.165897