Salivary gland tumors (SGTs) comprise a heterogeneous group of lesions, originating from distinct salivary gland portions and displaying a variety of histologies, and clinical behavior. Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the three most prevalent SGTs (Seethala, 2017, El-Naggar et al., 2017, Bradley, 2016, Bell and Hanna, 2012). PA is a benign SGT, composed by myoepithelial and epithelial cells and abundant stroma (Hernandez-Prera et al., 2021, Mendenhall et al., 2008). MEC originates in the excretory duct of the salivary gland and is characterized by epidermoid, mucous, and intermediate cells (Peraza et al., 2020, McHugh et al., 2012). ACC originates in the intercalated duct of the salivary gland and is subdivided into three histological patterns (cribriform, tubular, and solid) (Cantù, 2021, Coca-Pelaz et al., 2015).

Recently, many authors have been exploring the molecular profile of SGTs to understand their biology and pathogenesis, and to obtain new insights to facilitate personalized and targeted therapy. A myriad of genetic mutations and factors have been linked to salivary gland oncogenesis, tumor growth, and disease progression (Alame et al., 2020, Porcheri et al., 2020). The TGFβ cascade is among these factors, as it contributes to the maintenance of homeostasis and, in response to pathological processes, seems to play important roles as a tumor suppressor (Dillard et al., 2001; S. V. Lourenço & Lima, 2007a; S. V. Lourenço et al., 2004; Massagué, 2012; Wang et al., 2011).

The TGFβ pathway may operate as either a tumor suppressor or promoter (Principe et al., 2014). TGFβ is maintained in a latent complex, composed of fibrillin (FBN1) and latent TGFβ-binding protein (LTBP1), among other proteins. Upon activation by proteins and enzymes that include integrins (one example is ITGB6), TGFβ interacts with its specific membrane receptors (type I and II), promoting SMAD2/3 phosphorylation, SMAD4 recruitment, and nuclear translocation of the SMAD complex, thereby regulating target gene transcription. One of these target genes is c-MYC, which regulates the cell cycle (Aashaq et al., 2022, Peng et al., 2022, Massagué, 2012, Massagué et al., 2005) (Fig. 1).

Despite evidence that the TGFβ signaling pathway participates in neoplastic processes in many tissues and organs, its role in SGTs is only partially understood. We analyzed the expression of genes associated with the TGFβ signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) by real-time RT-PCR, in the most frequent SGTs to depict the cascade profile for future application in diagnostic technology, prognosis, and classification of these tumors.