scholarly journals Hedgehog Signaling Pathway and Autophagy in Cancer

2018 ◽  
Vol 19 (8) ◽  
pp. 2279 ◽  
Author(s):  
Xian Zeng ◽  
Dianwen Ju
Keyword(s):  
Drug Resistance ◽  
Hedgehog Signaling ◽  
Biological Process ◽  
Cellular Component ◽  
Hedgehog Signaling Pathway ◽  
Drug Resistant ◽  
Multiple Cancers ◽  
Success Stories ◽  
Cancer Types ◽  
Hh Signaling

Hedgehog (Hh) pathway controls complex developmental processes in vertebrates. Abnormal activation of Hh pathway is responsible for tumorigenesis and maintenance of multiple cancers, and thus addressing this represents promising therapeutic opportunities. In recent years, two Hh inhibitors have been approved for basal cell carcinoma (BCC) treatment and show extraordinary clinical outcomes. Meanwhile, a series of novel agents are being developed for the treatment of several cancers, including lung cancer, leukemia, and pancreatic cancer. Unfortunately, Hh inhibition fails to show satisfactory benefits in these cancer types compared with the success stories in BCC, highlighting the need for better understanding of Hh signaling in cancer. Autophagy, a conserved biological process for cellular component elimination, plays critical roles in the initiation, progression, and drug resistance of cancer, and therefore, implied potential to be targeted. Recent evidence demonstrated that Hh signaling interplays with autophagy in multiple cancers. Importantly, modulating this crosstalk exhibited noteworthy capability to sensitize primary and drug-resistant cancer cells to Hh inhibitors, representing an emerging opportunity to reboot the efficacy of Hh inhibition in those insensitive tumors, and to tackle drug resistance challenges. This review will highlight recent advances of Hh pathway and autophagy in cancers, and focus on their crosstalk and the implied therapeutic opportunities.

Role of knot (kn) in Wing Patterning in Drosophila

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1203-1212 ◽  
Author(s):  
Katerina Nestoras ◽  
Helena Lee ◽  
Jym Mohler
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Hedgehog Signaling Pathway ◽  
Posterior Compartment ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Hh Signaling ◽  
Embryonic Segmentation ◽  
Anterior Posterior

We have undertaken a genetic analysis of new strong alleles of knot (kn). The original kn1 mutation causes an alteration of wing patterning similar to that associated with mutations of fused (fu), an apparent fusion of veins 3 and 4 in the wing. However, unlike fu, strong kn mutations do not affect embryonic segmentation and indicate that kn is not a component of a general Hh (Hedgehog)-signaling pathway. Instead we find that kn has a specific role in those cells of the wing imaginal disc that are subject to ptc-mediated Hh-signaling. Our results suggest a model for patterning the medial portion of the Drosophila wing, whereby the separation of veins 3 and 4 is maintained by kn activation in the intervening region in response to Hh-signaling across the adjacent anterior-posterior compartment boundary.

scholarly journals Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Expression Levels ◽  
Pcos Group ◽  
Hh Signaling

Abstract The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

Relationship between Hedgehog Signaling Pathway and Drug Resistance of Poorly Differentiated Gliomas

2018 ◽  
Vol 164 (3) ◽  
pp. 356-361 ◽  
Author(s):  
S. A. Cherepanov ◽  
N. F. Grinenko ◽  
O. M. Antonova ◽  
P. B. Kurapov ◽  
I. I. Shepeleva ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Hedgehog Signaling Pathway ◽  
Poorly Differentiated

scholarly journals Aberrant Activation of the Hedgehog Signaling Pathway in Granulosa Cells from Patients with Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Qiongfang Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Control Group ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Pcos Group ◽  
Hh Signaling

Abstract The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cells. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals The Hedgehog Signaling Pathway in Ischemic Tissues

2019 ◽  
Vol 20 (21) ◽  
pp. 5270 ◽  
Author(s):  
Igor Giarretta ◽  
Eleonora Gaetani ◽  
Margherita Bigossi ◽  
Paolo Tondi ◽  
Takayuki Asahara ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tissue Regeneration ◽  
Hedgehog Signaling ◽  
Potential Role ◽  
Hedgehog Signaling Pathway ◽  
Pathological Conditions ◽  
Ischemic Tissue ◽  
Hh Signaling ◽  
The Brain

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.

scholarly journals Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Qiongfang Wu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Control Group ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Hh Signaling

Abstract Objective The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOSMethods The study was carried out by using RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysisResults The results found Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PT. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group (PT) were significantly higher than those in the control group (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cellsConclusions These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals The Roles of Hedgehog Signaling Pathway in Radioresistance of Cervical Cancer

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581988529 ◽  
Author(s):  
Chang Liu ◽  
Rensheng Wang
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Essential Role ◽  
Hedgehog Signaling Pathway ◽  
Advanced Cervical Cancer ◽  
New Strategy ◽  
The Relationship

Radiotherapy is an important treatment of cervical cancer, especially for advanced cervical cancer. According to research reports, Hedgehog signaling pathway plays an essential role in the growth, invasion, metastasis, recurrence, drug resistance, and radioresistance of cervical cancer. The components of Hedgehog signaling pathway could be biomarkers, related to progression and prognosis of cervical cancer. In addition, targeted therapy for Hedgehog signaling pathway is expected to become a new strategy for the treatment of radioresistant cervical cancer. This review summarizes the research status and progress of the relationship between radiation resistance and activation of Hedgehog signaling pathway in cervical cancer.

scholarly journals Hedgehog Signaling, a Critical Pathway Governing the Development and Progression of Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Jia Ding ◽  
Hui-Yan Li ◽  
Li Zhang ◽  
Yuan Zhou ◽  
Jian Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Relevant Literature ◽  
Hepatoma Cells ◽  
Signaling Molecules ◽  
Molecular Profile ◽  
Critical Pathway ◽  
Hh Signaling

Hedgehog (Hh) signaling is a classic morphogen in controlling embryonic development and tissue repairing. Aberrant activation of Hh signaling has been well documented in liver cancer, including hepatoblastoma, hepatocellular carcinoma (HCC) and cholangiocarcinoma. The present review aims to update the current understanding on how abnormal Hh signaling molecules modulate initiation, progression, drug resistance and metastasis of HCC. The latest relevant literature was reviewed with our recent findings to provide an overview regarding the molecular interplay and clinical relevance of the Hh signaling in HCC management. Hh signaling molecules are involved in the transformation of pre-carcinogenic lesions to malignant features in chronic liver injury, such as nonalcoholic steatohepatitis. Activation of GLI target genes, such as ABCC1 and TAP1, is responsible for drug resistance in hepatoma cells, with a CD133−/EpCAM− surface molecular profile, and GLI1 and truncated GLI1 account for the metastatic feature of the hepatoma cells, with upregulation of matrix metalloproteinases. A novel bioassay for the Sonic Hh ligand in tissue specimens may assist HCC diagnosis with negative α-fetoprotein and predict early microvascular invasion. In-depth exploration of the Hh signaling deepens our understanding of its molecular modulation in HCC initiation, drug sensitivity and metastasis, and guides precise management of HCC on an individual basis.

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