High expression of Sonic Hedgehog signaling pathway genes indicates a risk of recurrence of breast carcinoma

Abstract

BackgroundAbnormal activation of the Sonic Hedgehog (SHH) signaling pathway contributing to carcinogenesis of some organs has been reported in the literature. We hypothesize that activation of the SHH pathway contributes to the recurrence of breast carcinoma.MethodsFifty consecutive patients with invasive breast carcinoma following curative resection were enrolled in this prospective study. The ratios of messenger RNA (mRNA) expression for Sonic Hedgehog (SHH), patched homolog-1 (PTCH-1), glioma-associated oncogene-1 (GLI-1), and smoothened (SMOH) were measured between breast carcinoma tissue and paired noncancerous breast tissue. These ratios were compared with their clinicopathologic characteristics. These factors and the mRNA ratios were compared between patients with recurrence and those without recurrence.ResultsThe size of the invasive cancer correlated significantly with the ratio of SHH mRNA (P=0.001), that of PTCH-1 mRNA (P=0.005), and that of SMOH mRNA (P=0.021). Lymph node involvement correlated significantly with the ratio of SMOH mRNA (P=0.041). The correlation between Her-2 neu and the ratio of GLI-1 mRNA was statistically significant (P=0.012). Each ratio of mRNA of SHH, PTCH-1, GLI-1, and SMOH correlated significantly with cancer recurrence (P<0.001 for each).ConclusionWe suggest that high expression of SHH mRNA, PTCH-1 mRNA, GLI-1 mRNA, and SMOH mRNA in breast cancer tissue correlates with invasiveness and is a potential biomarker to predict postoperative recurrence.

Targeting the multidrug transporter Patched potentiates chemotherapy efficiency on adrenocortical carcinoma in vitro and in vivo

“…Indeed, aberrant activation of Hh signaling has been observed in many aggressive cancers, in particular in cells exhibiting resistance to chemotherapy such as cancer stem cells or tumor‐initiating cells . The Hh receptor Patched, whose expression is induced upon activation of the Hh pathway, is overexpressed in many cancers such as lung, breast, prostate, ovary, colon, brain, melanoma and myeloid leukemia (see the Human Protein Atlas website http://www.proteinatlas.org/ENSG00000185920-PTCH1/cancer). Recent studies even suggested Patched as an early marker of gastric and thyroid cancers .…”

Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15‐hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis‐associated cancer

“…These abnormal persistence or ectopic expression of Shh may stimulate an abnormal stem cell hyperplasia, a critical step in the neoplastic transition of these organs owing to its embryonic actions and mutagenic inflammation, though Shh relevant to inflammation varies by the cell/tissue type, location and overall environmental stresses. Regarding carcinogenesis, recent studies have implicated that continuous Shh signaling played a pathological role in the growth of various cancers such as medulloblastoma, basal cell skin carcinoma, squamous cell lung cancer, breast cancer, pancreatic cancer and CRC, where hedgehog was implicated in organogenesis and patterning of embryo during development stage . This is why, though Shh signaling is very critical to normal GI development, Shh has frequently been identified as target for GI cancers.…”

Heterogeneity of Hepatocellular Carcinoma

“…Gli, Smo and PTCH were found to be overexpressed in HCC patients (Che et al 2012;Jeng et al 2013;Zhang et al 2013). Lu et al (2012) reported that Shh treatment can stimulate Hedgehog signaling to promote HCC cell invasion and migration by increasing GLI1 expression.…”