**Floren G. Low, Kiran Shabir , James E. Brown, Roslyn M. Bill and Alice J. Rothnie \***

College of Health & Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK; low\_guy@hotmail.com (F.G.L.); shabirk@aston.ac.uk (K.S.); j.e.p.brown@aston.ac.uk (J.E.B.); R.M.Bill@aston.ac.uk (R.M.B.)

**\*** Correspondence: a.rothnie@aston.ac.uk

Received: 18 September 2020; Accepted: 7 October 2020; Published: 16 October 2020

**Abstract:** ABCC1 and ABCC4 utilize energy from ATP hydrolysis to transport many different molecules, including drugs, out of the cell and, as such, have been implicated in causing drug resistance. However recently, because of their ability to transport signaling molecules and inflammatory mediators, it has been proposed that ABCC1 and ABCC4 may play a role in the hallmarks of cancer development and progression, independent of their drug efflux capabilities. Breast cancer is the most common cancer affecting women. In this study, the aim was to investigate whether ABCC1 or ABCC4 play a role in the proliferation or migration of breast cancer cell lines MCF-7 (luminal-type, receptor-positive) and MDA-MB-231 (basal-type, triple-negative). The effects of small molecule inhibitors or siRNA-mediated knockdown of ABCC1 or ABCCC4 were measured. Colony formation assays were used to assess the clonogenic capacity, MTT assays to measure the proliferation, and scratch assays and Transwell assays to monitor the cellular migration. The results showed a role for ABCC1 in cellular proliferation, whilst ABCC4 appeared to be more important for cellular migration. ELISA studies implicated cAMP and/or sphingosine-1-phosphate efflux in the mechanism by which these transporters mediate their effects. However, this needs to be investigated further, as it is key to understand the mechanisms before they can be considered as targets for treatment.

**Keywords:** MRP1; MRP4; breast cancer; proliferation; migration; invasion; cAMP
