Speckle-type POZ adaptor protein (SPOP) and its role in cancer

Abstract

Proteasomal degradation is an essential regulatory mechanism for cellular homeostasis maintenance. The speckle-type POZ adaptor protein (SPOP) is part of the ubiquitin ligase E3 cullin-3 RING-box1 complex, responsible for the ubiquitination and proteasomal degradation of biomolecules involved in cell cycle control, proliferation, response to DNA damage, epigenetic control, and hormone signaling, among others. Changes in SPOP have been associated with the development of different types of cancer, since it can act as a tumor suppressor mainly in prostate, breast, colorectal, lung cancer and liver cancer, due to point mutations and/or reduced expression, or as an oncogene in endometrial cancer, in which function gain has been found, and in kidney cancer by protein overexpression. SPOP is a potential prognostic biomarker and a promising therapeutic target.

Determination of TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis

“…For example, some cases diagnosed with aggressive PCa correspond to misclassified patients that will suffer the side effects of a treatment that in reality was not necessary (Acosta et al, 2017; Lilja et al, 2008). Consequently, an increasing number of studies have been carried out to find PCa molecular subtypes that allow improving the classification of patients concerning prognosis using associated biomarkers, however, the relationship with prognosis is still unclear (Barbieri et al, 2014; Garcia‐Marques et al, 2022; Kulda et al, 2016; Lapointe et al, 2007; Montero‐Ovalle et al, 2021; Rubin et al, 2019; Sakellakis et al, 2022; Shoag et al, 2020; Song & Chen, 2018).…”

“…Differences in the frequency of these alterations could be due to the tumor heterogeneity reported in PCa, as well as the genetic variability among populations (Abeshouse et al, 2015; Li et al, 2020; Lowder et al, 2022; Magi‐Galluzzi et al, 2011). It is well recognized that for many types of cancer, including PCa (Bernasocchi & Theurillat, 2022; Hankey et al, 2020; Montero‐Ovalle et al, 2021; Nakazawa et al, 2022; Roshan‐Moniri et al, 2017), advances in their molecular characterization in subtypes have led to a better understanding of the implications in prognosis and precision medicine breakthroughs, tools that needs to be addressed for understudied populations such as Latinos, particularly in Colombia, given our high degree of genetic admixture and genetic variability across the country. In addition, the frequency of these alterations in Colombian men with PCa is unknown.…”