J Cancer 2022; 13(7):2374-2387. doi:10.7150/jca.65949 This issue
Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX, 78666, USA.
The Suppressor APC Domain Containing 2 (SAPCD2) gene, also known by its aliases p42.3 and c9orf140, encodes a protein with an approximate molecular weight of 42.3 kDa. It was initially recognized as a cell cycle-associated protein involved in mitotic progression. Since the initial discovery of this gene, emerging evidence has suggested that its functions extend beyond that of regulating cell cycle progression to include modulation of planar polarization of cell progenitors and determination of cell fate throughout embryonic development. The underlying mechanisms driving such functions have been partially elucidated. However, the detailed mechanisms of action remain to be further characterized. The expression level of SAPCD2 is high throughout embryogenesis but is generally absent in healthy postnatal tissues, with restored expression in adult tissues being associated with various disease states. The pathological consequences of its aberrant expression have been investigated, most notably in the development of several types of cancers. The role of SAPCD2 in tumorigenesis has been supported by in vitro, in vivo, and retrospective clinical investigations and the mechanisms underlying its oncogenic function have been partially revealed. The potential of SAPCD2 as a diagnostic marker and therapeutic target of cancers have also been explored and have shown great promise. However, many questions pertaining to its oncogenic mechanisms as well as its value as a diagnostic marker and therapeutic target remain to be answered. In addition to its function as an oncogene, an involvement of SAPCD2 in other pathological processes such as inflammation has also been implicated and provides additional directions that warrant future investigation. This article reviews the current understanding of the normal cellular functions of SAPCD2 and the relevance of SAPCD2 in disease development with a primary focus on tumorigenesis. The mechanisms that regulate p43.2 expression, including the potential role of microRNAs in regulating its expression, are also reviewed. To the best of our knowledge, we are the first to comprehensively review the published findings regarding the physiological and pathological functions of this gene.
Keywords: p42.3, SAPCD2, Cell Cycle, Cell Fate, Cancer, Metastasis.