Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells

Abstract

The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it is amplified in about 30% of triple negative breast (TNBC). Here, we have investigated the function of CSNK1D in triple negative cancer cell migration and metastasis.By using immunohistochemistry and in situ hybridization, we found that CNSK1D is highly expressed in primary tumor cells and in tumor cells invading lymphatic nodes compared to non-metastatic tumors. In vitro, knock-down of CSNK1D expression with specific shRNAs in the breast cancer cell line MDA-MB-231 markedly inhibited cancer cell proliferation, invasion and migration and affected the expression of the tight junction proteins claudin 1, occludin and the junction adhesion molecule A. In vivo, the inactivation of CSNK1D reduced lung metastasis in MDA-MB-231 breast cancer xenografts.Altogether, our results indicate that the downregulation of CSNK1D expression inhibits the proliferation and reduces the migration and the metastasis of breast cancer cells. As numerous inhibitors of CSNK1D are currently under development, this might represent an attractive therapeutic target for the treatment of TNBC.

Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells

“…Since CK1δ has been shown to regulate cell migration of triple negative breast cancer cells (40), we verified its possible involvement in the modulation of ovarian cancer cell motility. For this purpose, we firstly performed wound healing assay.…”

“…Previous work highlighted a negative impact of CK1δ inhibition on cell cycle progression and proper mitosis, eventually leading to apoptosis (18, 20, 29, 52). Moreover, in vivo breast and pancreatic tumor growth was delayed by CK1δ inhibitor administration (19, 30), and recently, impaired cell migration and metastases of triple negative breast cancer were also assessed (40).…”

“…A recent paper reported that CK1δ knockdown impaired breast cancer cell migration and invasion and upregulated epithelial markers such as claudin1 and occludin (40). Accordingly, specific knockdown of the CK1δ highly related kinase, CK1ε, demonstrated a 60–80% reduction in the migration ability of the EOC cell line SKOV3 (64).…”

CK1δ as a potential therapeutic target to treat bladder cancer

“…We also provided evidence that 13i HCl treatment or CK1δ knockdown inhibits RT112 cell migration ( Figure 6A, 6B). CK1δ reportedly activates Wnt/β-catenin in breast cancer [14,15] and CK1δ silencing reduces the migration and invasion of triplenegative breast cancer cells [32]. Importantly, either APC mutations or nuclear β-catenin accumulation are associated with poor outcome in patients with invasive bladder cancer [16].…”

The combination of an innovative dry powder for inhalation and a standard cisplatin-based chemotherapy in view of therapeutic intensification against lung tumours

“…Bioluminescence imaging of the whole mice was performed two times a week to follow in vivo tumour growth (primary tumour and metastases) and was expressed as the tumour growth % relative to day 3. Bioluminescence imaging was performed by means of a Photon Imager Optima (Biospace Lab, France) that dynamically counted the emitted photons for at least 25 min, with the mice under anaesthesia (4% and 2% isoflurane for initiation and maintenance, respectively) and after subcutaneous administration of 150 mg/kg of D-luciferin (Promega, Leiden, Netherlands) [23]. Image analysis was performed with M3Vision software (Biospace Lab).…”