Xin Ling, Liu Chang, Liu Yinhua, Mansel Robert E, Ruge Fiona, Davies Eleri, Jiang Wen G, Martin Tracey A
Breast Disease Centre of Peking University First Hospital Beijing, PR China.
School of Medicine, Cardiff University Heath Park, Cardiff, United Kingdom.
Am J Cancer Res. 2021 Jul 15;11(7):3537-3557. eCollection 2021.
Salt-inducible kinases (SIKs), belonging to an AMP-activated kinase (AMPK) family, have an evolving role in tumourigenesis and metastasis in many solid tumours. However, the function of SIKs in breast cancer is not fully established. Here, we systematically elucidated the function of SIK family members in breast cancer. In clinical cohort of breast cancer, the expression of SIK1, SIK2 and SIK3 increased expression of SIKs was associated with good clinical outcome in breast cancer cohort. , reduced expression of SIK2 and SIK3, by way of knockdown increased the proliferation of breast cancer cells. However, SIK2 and SIK3 had contrasting effects on adhesion in breast cancer cells. Knockdown of SIK2 only enhanced the adhesion of triple negative breast cancer cell, while knockdown of SIK3 can decrease the adhesion of both MDA-MB-231 and MCF-7 cells. Interestingly, knockdown of SIK1 and SIK3 was seen to increase the invasion of MDA-MB-231 cells. Furthermore, reduced SIKs, even triple knockdown of SIK1, SIK2 and SIK3 rendered the breast cancer cells to confer chemoresistance to paclitaxel and cisplatin. Collectively, the study reports that SIKs are actively involved in regulating the aggressive functions of breast cancer cells and influence the clinical course of the patients with breast cancer that they molecules are potential prognostic factors and chemotherapy biomarkers.
盐诱导激酶（SIKs）属于AMP激活激酶（AMPK）家族，在许多实体瘤的肿瘤发生和转移中发挥着不断演变的作用。然而，SIKs在乳腺癌中的功能尚未完全明确。在此，我们系统地阐明了SIK家族成员在乳腺癌中的功能。在乳腺癌临床队列中，SIK1、SIK2和SIK3的表达增加，SIKs表达增加与乳腺癌队列中的良好临床结局相关。通过敲低降低SIK2和SIK3的表达会增加乳腺癌细胞的增殖。然而，SIK2和SIK3对乳腺癌细胞的黏附具有相反的作用。敲低SIK2仅增强三阴性乳腺癌细胞的黏附，而敲低SIK3可降低MDA-MB-231和MCF-7细胞的黏附。有趣的是，敲低SIK1和SIK3会增加MDA-MB-231细胞的侵袭。此外，降低SIKs，甚至同时敲低SIK1、SIK2和SIK3会使乳腺癌细胞对紫杉醇和顺铂产生化学抗性。总体而言，该研究报告称，SIKs积极参与调节乳腺癌细胞的侵袭性功能，并影响乳腺癌患者的临床病程，表明它们是潜在的预后因素和化疗生物标志物。
