PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell carcinoma

Saito, Tsuyoshi; Mitomi, Hiroyuki; Imamhasan, Abdukadir; Hayashi, Takuo; Kurisaki-Arakawa, Aiko; Mitani, Keiko; Takahashi, Michiko; Kajiyama, Yoshiaki; Yao, Takashi

doi:10.1093/mutage/geu072

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…Conversely, mutations impacting SUFU function in BCC are rare [187]. Similarly, PTCH1 somatic mutations and loss of heterozygosity have been described in transitional cell carcinoma (TCC) of the bladder and esophageal squamous cell carcinoma [158,[188][189][190].…”

Section: Type I Signaling-autonomous and Shh Ligand-independentmentioning

confidence: 99%

Hedgehog Signaling and Truncated GLI1 in Cancer

Doheny

Manore

Wong

et al. 2020

Cells

130

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The hedgehog (HH) signaling pathway regulates normal cell growth and differentiation. As a consequence of improper control, aberrant HH signaling results in tumorigenesis and supports aggressive phenotypes of human cancers, such as neoplastic transformation, tumor progression, metastasis, and drug resistance. Canonical activation of HH signaling occurs through binding of HH ligands to the transmembrane receptor Patched 1 (PTCH1), which derepresses the transmembrane G protein-coupled receptor Smoothened (SMO). Consequently, the glioma-associated oncogene homolog 1 (GLI1) zinc-finger transcription factors, the terminal effectors of the HH pathway, are released from suppressor of fused (SUFU)-mediated cytoplasmic sequestration, permitting nuclear translocation and activation of target genes. Aberrant activation of this pathway has been implicated in several cancer types, including medulloblastoma, rhabdomyosarcoma, basal cell carcinoma, glioblastoma, and cancers of lung, colon, stomach, pancreas, ovarian, and breast. Therefore, several components of the HH pathway are under investigation for targeted cancer therapy, particularly GLI1 and SMO. GLI1 transcripts are reported to undergo alternative splicing to produce truncated variants: loss-of-function GLI1ΔN and gain-of-function truncated GLI1 (tGLI1). This review covers the biochemical steps necessary for propagation of the HH activating signal and the involvement of aberrant HH signaling in human cancers, with a highlight on the tumor-specific gain-of-function tGLI1 isoform.

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Section: Type I Signaling-autonomous and Shh Ligand-independentmentioning

confidence: 99%

Hedgehog Signaling and Truncated GLI1 in Cancer

Doheny

Manore

Wong

et al. 2020

Cells

130

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“…In some tumors Hh pathway is activated in a ligand-independent manner by inactivating mutations of Ptch1 79 , 80 . Ptch1, as a tumor suppressor that inhibits Smo, were reported that exhibits a higher expression in well and moderate differentiated HCC, but a lower expression in poorly differentiated HCC 81 .…”

Section: Hh Signaling In Liver Cancersmentioning

confidence: 99%

Role of canonical Hedgehog signaling pathway in liver

Gao¹,

Zhang²,

Zhang³

et al. 2018

Int. J. Biol. Sci.

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Hedgehog (Hh) signaling pathway plays an important role in embryonic development. It becomes reactivated in many types of acute and chronic liver injuries. Hh signaling is required for liver regeneration, regulates capillarisation, controls the fates of hepatic stellate cells, promotes liver fibrosis and liver cancers. In this review, we summarize the current knowledge of the role of canonical Hh signaling pathway in adult liver. This help to understand the pathogenesis of liver diseases and find out the new effective targeted therapeutic strategies for liver diseases treatments.

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“…28 Besides, some studies indicated that the target gene of Hh, including Gli1 and PTCH1, can be identified as an independent adverse prognostic factor in ESCC. 26,29 Collectively, the activation of SHH signaling is closely linked to the oncogenesis and development of esophageal cancers, researches about their correlation may offer new ideas for the treatment of ESCC.…”

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confidence: 99%

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

Zhao

Guo

et al. 2020

Cancer Medicine

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Esophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer‐associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs‐derived exosomes have a role in the progression of ESCC is largely unknown. Here, we find that Sonic Hedgehog (SHH) is highly expressed in CAFs lysis solution, conditioned medium of cultured CAFs (CAF‐CM) and CAFs‐derived exosomes, and esophageal cancer cell lines educated by CAF‐CM and CAFs‐derived exosomes can improve their growth and migration abilities in vitro and in vivo. Besides, those effects can be partly neutralized by cyclopamine, inhibitor of the Hedgehog signaling pathway. Thus, our research elucidates the crucial role of CAFs‐derived exosomes in the growth and progression of ESCC, and may open up new avenues in the treatment of ESCC.

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PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell carcinoma

Cited by 8 publications

References 30 publications

Hedgehog Signaling and Truncated GLI1 in Cancer

Hedgehog Signaling and Truncated GLI1 in Cancer

Role of canonical Hedgehog signaling pathway in liver

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

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