The Role of Smoothened in Cancer

Abstract

Smoothened (SMO) belongs to the Hedgehog (HH) signaling pathway, which regulates cell growth, migration, invasion and stem cells in cancer. The HH signaling pathway includes both canonical and noncanonical pathways. The canonical HH pathway functions through major HH molecules such as HH ligands, PTCH, SMO and GLI, whereas the noncanonical HH pathway involves the activation of SMO or GLI through other pathways. The role of SMO has been discussed in different types of cancer, including breast, liver, pancreatic and colon cancers. SMO expression correlates with tumor size, invasiveness, metastasis and recurrence. In addition, SMO inhibitors can suppress cancer formation, reduce the proliferation of cancer cells, trigger apoptosis and suppress cancer stem cell activity. A better understanding of the role of SMO in cancer could contribute to the development of novel therapeutic approaches.

Anticancer Mechanism of Curcumin on Human Glioblastoma

“…Additionally, the overexpression of Smo is significantly associated with poor prognosis in GBM patients [ 131 ]. Smo expression inhibition, which suppresses GBM proliferation, migration, invasion, and tumorigenesis, further supports this observation [ 132 ].…”

Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme

“…Additionally, to better acquire knowledge of the processes the TFs participate in each of the cell types, we performed a pathway enrichment analysis. This evaluation revealed that in TP astrocyte, TFs ZNF878 and CREB3L4 are involved in highest number of processes such as signal transduction downstream of smoothened protein which is involved in hedgehog signaling [36] , activation of phospholipase C activity and peroxisome, positive regulation of translation, respectively ( Fig. 7 A) .…”

Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

“…It is well known that SMO activates the Gli1 in the canonical Hedgehog pathway 20 , 24 . To investigate whether SMO is implicated in Rab1A-mediated Gli1 upregulation, we detected SMO protein expression in Rab1A-depleted and Rab1A-overexpressed CRC cells.…”

“…The Hedgehog (HH) signaling pathway is a conserved pathway involved in cell growth and tissue patterning 18 – 20 . In mammals, HH signaling initiates with binding of one of the three ligands (Indian Hedgehog (IHH), Sonic Hedgehog (SHH) and Desert Hedgehog (DHH)) to the protein patched homolog (PTCH), causing the release of the suppressed transmembrane protein Smoothened (SMO).…”