Hedgehog signaling pathway originally identified in the fruit fly Drosophila is an evolutionarily conserved signaling mechanism with crucial roles in embryogenesis, growth and patterning. It exerts its biological effect through a signaling mechanism that terminates at glioma-associated oncogene (GLI) transcription factors which alternate between activator and repressor forms and mediate various responses. The important components of the pathway include the hedgehog ligands (SHH), the Patched (PTCH) receptor, Smoothened (SMO), Suppressor of Fused (SuFu) and GLI transcription factors. Activating or inactivating mutations in key genes cause uncontrolled activation of the pathway in a ligand independent manner. The ligand-dependent aberrant activation of the hedgehog pathway causing overexpression of hedgehog pathway components and its target genes occurs in autocrine as well as paracrine fashion. In adults, aberrant activation of hedgehog signaling has been linked to birth defects and multiple solid cancers. In this review, we assimilate data from recent studies to understand the mechanism of functioning of the hedgehog signaling pathway, role in cancer, its association in various solid malignancies and the current strategies being used to target this pathway for cancer treatment.

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Background: There are scarce data on the prevalence of thyroid disorders and urinary iodine status among tribal populations of India, with no reported data from Kashmir valley. Conclusion:These novel data on iodine and thyroid status among a tribal population of India generally inhabiting in remote sub-Himalayan belts demonstrate high prevalence of subclinical hypothyroidism (SCH) with persistent iodine deficiency. These preliminary data may warrant large well-designed studies to carry out comprehensive assessment of the problem in this high-risk and marginalized population.

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Smoothened (SMO) is a significant signalling protein which functions as a key transducer for the hedgehog signalling pathway, an important signalling mechanism with key roles in development and oncogenesis. The correlation of expression dynamics of SMO with pancreatic and colorectal cancer genesis has been known but with ambiguity. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SMO in pancreatic and colorectal cancers in our population and assessed relationship with various clinicopathological parameters. Surgically resected tumour and adjacent histologically normal tissues from 33 and 61 pancreatic and colorectal cancer patients were investigated in the present study. Expression of SMO was analysed by quantitative real-time polymerase chain reaction and immunohistochemistry. At mRNA level, SMO was overexpressed in 72.72% (24 of 33) and 50.81% (31 of 61) of the pancreatic and colorectal cancer cases as compared with their adjacent normal tissues. SMO immunohistochemical analysis revealed nuclear localization and overexpression was observed in 51.51% (17 of 33) and 40.98% (25 of 61) of pancreatic and colorectal cancer tissues. SMO overexpression was significantly associated with smoking, late-stage disease and lymph node metastasis in patients with Colorectal cancer. Our results showed that SMO is dysregulated in pancreatic and colorectal cancers and may be considered as a target in cancer therapeutics.