LIMCH1-related genes demonstrate different invasive potential of morphological structures of breast cancer

Abstract

Abstract Background Tumor cell invasion is an integral component of breast cancer progression. In cell motility, including tumor cells, involves the actin cytoskeleton, which is a complex system with many regulatory points. The new tumor supressor protein LIMCH1, which has an actin binding domain, is a promising molecular target to suppress invasion. The presented work is aimed at revealing features of LIMCH1 expression in cells that demonstrate various forms of invasion in breast cancer. Methods The study included 37 patients with invasive breast carcinoma of a non-specific type (all molecular types). A list of genes was formed and molecular networks associated with LIMCH1 signaling were constructed. Using the previously obtained unique data of transcriptomic microarray profiling of various morphological structures of invasive breast carcinoma of a non-specific type (GSE80754), differentially expressed genes associated with LIMCH1 in the morphological structures were annotated. Results Tumor cells can move collectively or individually. The structural diversity of the infiltrative component of invasive breast carcinima represent an attractive model for investigation of tumor cell invasion. The solid and trabecular structures, may be considered as a morphological manifestation of collective cell invasion. Discrete groups and single tumor cells, are an example of individual cell invasion. Analyze of expression LIMCH1-related genes in different morphological structures showed that proinvasive XPO1 gene downregulated in trabecular structures. In single tumor cells expression of ODF2 gene that had stimulation activity for prolifiration were supressed comparing with trabecular structures. SH3KBP1 gene in solid structures is upregulated comparing other structures. Well known that SH3KBP1 revents epidermal growth factor receptor degradation. Also, HuR gene expression were upregulated in solid and trabecular structures comparing single tumor cells. Conclusions The obtained data showed that the morphological structures of invasive breast carcinoma have significant functional heterogeneity associated with the manifestations of invasion regulated by the LIMCH1 protein. The study was supported by RFBR (#18-515-16001). Legal entity responsible for the study Tomsk National Research Medical Center. Funding Russian Foundation for Basic Research (project #18-515-16001). Disclosure All authors have declared no conflicts of interest.