SPANX Regulation of LAMIN A/C Network: Perspectives in Cancer and Laminopathies

Abstract

216 Cancer/testis antigens (CTA) are tumor antigens whose expression is normally restricted to the testis. More than half of CTA genes are located on the X chromosome and form a branch called X-CTA [1]. Unlike the remaining CTA genes located throughout the genome, multigene X-CTA families are present as clusters on the X chromosome. Among them, the Sperm Protein Associated with the Nucleus on the X chromosome (SPANX) family is composed by five members [SPANX-A1, -A2 (-A1 and -A2 being two copies of the same gene), -B1, -C and -D]. As SPANX proteins are highly homologous and cannot be distinguished by antibody-based techniques, unless stated otherwise, hereafter we will use the term “SPANX” to refer to these five proteins. SPANX proteins are expressed post-meiosis in round and elongating spermatids [2], and their expression positively correlates with male fertility measured by pregnancy rate [3]. SPANX function in spermatids and spermatozoa is poorly characterized. However, cell fractionation analysis revealed that SPANX is abnormally distributed in samples with low spermatozoa motility [4] suggesting that SPANX is related to this process. Furthermore, identification of SPANX partners in spermatozoa has revealed proteins functioning in nuclear organization, mitochondrial metabolism and flagellar motility [5]. The discovery that SPANX genes are expressed in tumor cells was reported in a search for metastasis-specific genes in the melanoma line 1F6m, a metastatic variant of the parental 1F6 line [6]. Since then, SPANX gene expression has been observed in numerous malignancies, including breast cancer and hematological malignancies, as well as melanoma [6,7].