ORIGINAL ARTICLE Alterations in SCAI Expression during Cell Plasticity, Fibrosis and Cancer Ákos Gasparics 1 & Gábor Kökény 1 & Attila Fintha 2 & Rita Bencs 1 & Miklós M. Mózes 1 & Emese Irma Ágoston 3 & Anna Buday 1 & Zoltán Ivics 4 & Péter Hamar 1 & Balázs Győrffy 5,6 & László Rosivall 1 & Attila Sebe 1,4 Received: 20 June 2017 /Accepted: 9 August 2017 /Published online: 16 August 2017 # Arányi Lajos Foundation 2017 Abstract Suppressor of cancer cell invasion (SCAI) has been originally characterized as a tumor suppressor inhibiting metas- tasis in different human cancer cells, and it has been suggested that SCAI expression declines in tumors. The expression pat- terns and role of SCAI during physiological and pathophysio- logical processes is still poorly understood. Earlier we demon- strated that SCAI is regulating the epithelial-mesenchymal tran- sition of proximal tubular epithelial cells, it is downregulated during renal fibrosis and it is overexpressed in Wilms’ tumors. Here we bring further evidence for the involvement of SCAI during cell plasticity and we examine the prognostic value and expression patterns of SCAI in various tumors. SCAI prevented the activation of the SMA promoter induced by an- giotensin II. SCAI expression decreased in a model of endothelial-mesenchymal transition and increased during iPS reprogramming of fibroblasts. During renal fibrosis SCAI ex- pression declined, as evidenced in a rat model of renal trans- plant rejection and in TGF-β1 overexpressing transgenic mice. High expression of SCAI correlated with better survival in patients with breast and lung cancers. Intriguingly, in the case of other cancers (gastric, prostate, colorectal) high SCAI ex- pression correlated with poor survival of patients. Finally, we bring evidence for SCAI overexpression in colorectal cancer patients, irrespective of stage or metastatic status of the disease, suggesting a diverse role of SCAI in various diseases and cancer. Keywords Suppressor of cancer cell invasion (SCAI) . Epithelial-mesenchymal transition (EMT) . Cell plasticity . Fibrosis . Cancer Introduction SCAI (Suppressor of Cancer Cell Invasion) is a relatively recent- ly characterized interacting partner of Myocardin Related Transcription Factor/Serum Response Factor (MRTF/SRF). Consistent with the role of MRTFs in tumor progression and epithelial-mesenchymal transition (EMT) [1–3], SCAI acts through the transcriptional repression of the MKL-SRF complex [4], and as such, through the inhibition of CArG dependent gene expression [5]. Consistent with a tumor suppressor role, SCAI inhibits tumor cell invasion, β 1 -integrin expression [4] and EMT [5]. The role of SCAI during EMT is well established, SCAI regulates the expression of several markers and regulators of EMT. It inhibits TGF-β1 induced expression of CTGF, calponin and SMA. It also prevents TGF-β1 induced E-cadherin down- regulation, through regulating Snail expression [6]. SCAI direct- ly regulates TWIST expression, and SCAI downregulation led to transcriptional activation of the Wnt/β-catenin pathway [6]. SCAI controls gene expression by the interaction with the SWI/SNF complex and SWI/SNF could be a downstream medi- ator for SCAI signaling [7]. MRTF also contributes to dendritic * Attila Sebe sebe.attila@med.semmelweis-univ.hu 1 Department of Pathophysiology, Semmelweis University, Nagyvarad ter 4, rm 1810, Budapest 1089, Hungary 2 2nd Department of Pathology, Semmelweis University, Budapest, Hungary 3 1st Department of Surgery, Semmelweis University, Budapest, Hungary 4 Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany 5 MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary 6 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary Pathol. Oncol. Res. (2018) 24:641–651 DOI 10.1007/s12253-017-0293-4