Gasparics Ákos, Kökény Gábor, Fintha Attila, Bencs Rita, Mózes Miklós M, Ágoston Emese Irma, Buday Anna, Ivics Zoltán, Hamar Péter, Győrffy Balázs, Rosivall László, Sebe Attila
Department of Pathophysiology, Semmelweis University, Nagyvarad ter 4, rm 1810, Budapest, 1089, Hungary.
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Pathol Oncol Res. 2018 Jul;24(3):641-651. doi: 10.1007/s12253-017-0293-4. Epub 2017 Aug 16.
Suppressor of cancer cell invasion (SCAI) has been originally characterized as a tumor suppressor inhibiting metastasis in different human cancer cells, and it has been suggested that SCAI expression declines in tumors. The expression patterns and role of SCAI during physiological and pathophysiological processes is still poorly understood. Earlier we demonstrated that SCAI is regulating the epithelial-mesenchymal transition 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 angiotensin II. SCAI expression decreased in a model of endothelial-mesenchymal transition and increased during iPS reprogramming of fibroblasts. During renal fibrosis SCAI expression declined, as evidenced in a rat model of renal transplant 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 expression 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.
癌细胞侵袭抑制因子（SCAI）最初被表征为一种肿瘤抑制因子，可抑制不同人类癌细胞的转移，并且有研究表明SCAI在肿瘤中的表达会下降。目前对于SCAI在生理和病理生理过程中的表达模式及作用仍知之甚少。此前我们证明SCAI可调节近端肾小管上皮细胞的上皮-间质转化，在肾纤维化过程中其表达下调，而在肾母细胞瘤中过表达。在此我们为SCAI参与细胞可塑性提供了进一步证据，并研究了SCAI在各种肿瘤中的预后价值和表达模式。SCAI可阻止血管紧张素II诱导的平滑肌肌动蛋白（SMA）启动子的激活。在内皮-间质转化模型中SCAI表达降低，而在成纤维细胞的诱导多能干细胞（iPS）重编程过程中表达增加。在肾纤维化过程中，SCAI表达下降，这在肾移植排斥反应的大鼠模型以及过表达转化生长因子-β1（TGF-β1）的转基因小鼠中得到证实。SCAI的高表达与乳腺癌和肺癌患者的较好生存率相关。有趣的是，在其他癌症（胃癌、前列腺癌、结直肠癌）中，SCAI的高表达与患者的较差生存率相关。最后，我们证明结直肠癌患者中存在SCAI过表达，无论疾病的分期或转移状态如何，这表明SCAI在各种疾病和癌症中具有不同作用。
