## 1 Introduction  
The evolutionary highly conserved Hedgehog-GLI (HH-GLI) signaling pathway plays an essential role in many aspects of embryonic development, and in adult organisms is mainly responsible for stem cell maintenance and tissue homeostasis [1]. In mammals, the main representatives of the pathway are three hedgehog ligands: desert, Indian, and sonic hedgehog (DHH, IHH, and SHH, respectively); two transmembrane receptors (FTC1 and PTC2); the transmembrane G protein-coupled co-receptor SMO; and a family of transcriptional factors GLI that are regulated by a suppressor of fused (SUFU) protein [2]. The binding of one HH ligand to PTC receptor terminates its repression of SMO and this depression causes the release of GLIs from SUFU. GLIs are then translocated to the nucleus, where they regulate the transcription of target genes that are involved in many cellular processes, such as cell cycle regulation and proliferation, cell survival and self-renewal, cell adhesion, epithelial-mesenchymal transition, angiogenesis and pathway autoregulation [3]. Described activation is considered as ligand-dependent canonical signalization. HH proteins are morphogens and as such control numerous processes during embryonic development. All HH proteins expressed in mammals are thought to have similar physiological functions, and differences in their roles during development arise from different expression patterns [4]. SHH, however, is the most widely expressed compared to others and is considered to be the main ligand. After translation, HH proteins undergo several processing steps that result in an active ligand. HH proteins contain an N-terminal signaling domain and a C-terminal auto-processing domain. To become fully active, the C-terminal domain autocatalytically initiates cleavage of the protein and addition of cholesterol to the C-terminus of the signaling domain. Furthermore, hedgehog acyltransferase (HHAT) binds the palmitoyl group to the N-terminus of the signaling domain. The mature signal peptide is often designated as HhNp or, in the case of SHH, as SHH-N [5]. These two lipid posttranslational modifications (PTMs) are essential for both the activity and the regulation of HHs spread through tissues [6; 7]. Aberrant activation of the HH-GLI pathway in adult cells, caused by either genetic [8] or epigenetic [9] factors, has been linked with the development of various tumor types, including hormone-sensitive cancers, like breast, ovarian, uterine or prostate cancer [10; 11; 12; 13]. Hormone-sensitive or hormone-dependent cancers are those whose growth and survival are dependent on hormones that bind to their specific receptors. Both endogenous and exogenous hormones drive cell proliferation and increase the number of cell divisions, resulting in the growth and spread of tumor cells [14]. These four aforementioned cancers are the main types of hormone-sensitive cancers, and they depend on sex steroid hormones--estrogens, progesterone, or androgens. One of the main reasons why tumor cells are hormone-sensitive is because they often overexpressed sex hormone receptors (SHRs) in particular, along with estrogen receptors (ER), progesterone receptors (PR), or androgen receptors (AR), which attests to their fundamental role in the pathogenesis and progression of hormone-dependent tumors [15]. SHRs, and specifically their nuclear forms, belong to the steroid hormone receptor subfamily of the nuclear receptor superfamily. They are transcription factors and their structural domains enable affinity binding to both their ligands (sex hormones) and response elements of their target genes, which enables a direct regulation of target gene transcription [16]. SHRs regulate the transcription of genes that control many different biological processes, like cell proliferation, development, metabolism, and reproduction [17].