G-protein coupled receptor-associated sorting protein 1 (GASP-1), a ubiquitous tumor marker, promotes proliferation and invasion of triple negative breast cancer

Abstract

We have identified the novel protein GASP-1 (G protein coupled receptor-associated sorting protein 1) that appears to be a universal cancer marker and the expression of which in tumor tissue and patient sera is predictive of cancer severity (Tuszynski et al. 2011; Zheng et al. 2012; Zheng 2013; Chang and Tuszynski, 2020). In preliminary results we discovered that a GASP-1 antibody inhibited the growth of the triple negative breast cancer cell line MDA-MB-231 and transient reduction of GASP-1 in these cells decreased their proliferation. To further substantiate these results, we over and under-expressed GASP-1 in stable clones of MDA-MB-231 cells and evaluated their growth and invasive activities. Cells under-expressing GASP-1 failed to grow after 4 days in culture and eventually died. In contrast GASP-1 expressing cells grew exponentially. Similarly, GASP-1 under-expressing cells formed 30% fewer colonies in soft agar as compared to controls and whereas GASP-1 over-expressing cells formed 2-fold more colonies than controls. In tumor cell invasion assays GASP-1 over-expressing cells were over 10-fold more invasive than controls whereas GASP-1 under-expressing cells were over 10-fold less invasive than controls. In IHC staining studies of breast cancer cells, we found that the overexpressed GASP-1 appear in granules of different sizes that are directly correlated with cancer invasiveness. Our results strongly indicate that GASP-1 promotes proliferation and invasion of the triple negative breast cancer cell line MDA-MB-231 and targeting GASP-1 for treatment of breast cancer is indicated.