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Rhabdoid Tumor : Role of SMARCB1 (INI1)

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Interaction of SMARCB1 with Sonic Hedgehog Pathway: The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. It influences tumorigenesis, tumor progression and therapeutic response.

Hedgehog signal transduction is initiated by the binding of Hh proteins to the Patched 1 protein (PTC). SMARCB1 normally down regulates Shh pathway by repressing glioma-associated oncogene homolog (GLI) family of zinc finger transcription factors (GLI1, GLI2, and GLI3) as well as PTCH1 (that codes for PTC). SMARCB1-deficient tumors show overexpression of GLI and other proteins associated with activation of Shh pathway. Conversely, reintroduction of SMARCB1/INI1 in malignant rhabdoid tumor cell lines represses GLI1 expression.

Image source: Kalimuthu SN, Chetty R. Gene of the month: SMARCB1. J Clin Pathol 2016; 69:484-489; used under Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license.

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