Los tumores anexiales de la piel representan un grupo heterogéneo de entidades de baja frecuencia de presentación. Su origen es controvertido, quizás a partir de células madres pluripotenciales, aceptándose principalmente dos líneas embriológicas: pilosebáceo-apócrina y ecrina. Se los clasifica en cuatro grupos principales: tumores del folículo piloso, tumores sebáceos, tumores apócrinos y tumores ecrinos. Su distribución anatómica refleja áreas con mayor densidad de anexos cutáneos, presentándose en forma única o múltiple.

SALL2 is a transcription factor, member of the Spalt gene family, which has been associated with development, differentiation and cancer. Interestingly, SALL2 deficiency leads to failure of both closure of the optic fissure and neurite outgrowth, suggesting a positive role for SALL2 in cell migration. Conversely, recent studies in ovarian cancer cells suggest that SALL2 plays a negative role in cell migration. Cell migration is a multistep process that involves cellular polarization, formation of membranous protrusions, assembly and disassembly of focal adhesions and cell traction. Hence, understanding the role of SALL2 in cell migration will be relevant to comprehend its function in physiology and disease. Here, we evaluated the role of SALL2 in cell migration, by using immortalized Sall2 knockout (KO) and Sall2 wild type Mouse Embryonic Fibroblasts (MEFs), and gain/loss of function experiments. To this end, we measured the effects of SALL2 in different aspects of cell migration, including wound healing in monolayers, cell adhesion, cell detachment, focal adhesion dynamics, as well as by immunofluorescence assays. For mechanistic insights we used Western blot, real time PCR, luciferase reporter assays, and bioinformatics analysis. Data were compared in unpaired Student’s t-tests by using the GraphPad Prism software. Our data indicate that SALL2 positively regulates cell migration by promoting cell polarization, cell detachment, and increased turnover of focal adhesions. Sall2-deficiency as well as Sall2 knockdown by short hairpin RNA led to reduced cell migration and focal adhesion dynamics. Accordingly, restored SALL2 expression through a TET-ON system in the Sall2 KO MEFs recovered cell migratory capabilities. Interestingly, SALL2 accelerated focal adhesion disassembly after nocodazole- wash out treatment. In addition, in a cell spreading context and after nocodazole treatment, SALL2 augmented Focal Adhesion Kinase (FAK) autophosphorylation on Y397 and promoted the expression of integrins b1 and a6. Taken together, our data suggest that SALL2 promotes MEF cell migration by modulating focal adhesion dynamics via a mechanism involving augmented expression of integrins b1 and a6. Since deregulation of cell migration promotes tumor formation, invasion and metastasis, our findings indicate that deregulation of SALL2 may be associated with the disease. Funded by FONDECYT 1191172, FONDECYT 1180495; FONDAP 15130011 Citation Format: Elizabeth Riffo, Mario Palma, Catalina Alarcon, Ariel Castro, Vicente Torres, Roxana Pincheira. The SALL2 transcription factor promotes cell migration and focal adhesion turnover via regulation of integrin expression [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C131. doi:10.1158/1535-7163.TARG-19-C131