The Hedgehog (Hh) signaling pathway plays a crucial role in the development of the gastrointestinal tract and maintenance of the physiologic function of the stomach. Aberrantly activated Hh signaling is implicated in carcinogenesis as well as maintenance of cancer stem cells.  Hh signaling is often aberrantly activated and plays an important role in the inflammation and carcinogenesis of gastric epithelial cells.  Abnormal HH signaling activation not only causes uncontrolled proliferation of tumor cells but also contributes to the establishment of an immunosuppressive TME by regulating macrophage and T cell-dependent immune responses as well as the expression of tumor-related inflammatory factors. HH signaling activation is associated with certain GID, including Pallister–Hall syndrome, gut mal rotation and gastric cancer. In GIC, the expression of SHH and IHH signaling pathway components and their target genes is upregulated. Specifically, the expression of GLI1 is usually correlated with the degree of malignancy of gastric cancer, especially with lymph node metastasis

1. Hedgehog Signalling in Gastric Cancer
NAME:- SAYANTIKA SADHU
ROLL. NO:- 27720222014
REGN. NO:- 222772310026 OF 2022-23
STREAM:- MASTER OF PHARMACY (PHARMACOLOGY)
YEAR/SEMESTER:- 1ST YEAR/2ND SEMESTER
INSTITUTE:- NSHM KNOWLEDGE CAMPUS, KOLKATA-277

2. History of Hedgehog
The Drosophila Hedgehog (Hh) gene was identified as
one of several genes important for creating the
differences between the anterior and posterior parts of
individual body segments. The fly Hh gene was
independently cloned in 1992 by the labs of Jym
Mohler, Philip Beachy, Thomas B. Kornberg and Saigo
Kaoru.

3. Mechanism of Hedgehog in Larva

4. Genes of Hedgehog Proteins
 Sonic Hedgehog:- Involved in many
developmental processes.
 Desert Hedgehog:- expressed in
sertoli cells of testes
 Indian Hedgehog:- expressed in
guts and chondrocytes
They are all present in Vertebrates

5. Outline of Hedgehog Signalling Pathway

6. Outline of Hedgehog Signalling in Cancer

7. Gastric Cancer and it’s stages
Gastric cancer consists of two
pathological variants, intestinal and
diffuse. The intestinal-type is the end-
result of an inflammatory process that
progresses from chronic gastritis to
atrophic gastritis and finally to intestinal
metaplasia and dysplasia.

8. Symptoms of Gastric Cancer

9. Formation of
Gastric Cancer

10. Pathogenic mechanism of Hedgehog Signaling in Gastric Cancer
The Hedgehog (Hh) signaling pathway
plays a crucial role in the development
of the gastrointestinal tract and
maintenance of the physiologic function
of the stomach. Aberrantly activated Hh
signaling is implicated in carcinogenesis
as well as maintenance of cancer stem
cells.

11. A simplified model of the mammalian Hh pathway

12. Molecular sites targeted by Hh signaling pathway inhibitors

13. The role of HH signaling in gastrointestinal carcinogenesis
HH signaling activation is associated with certain GID, including Pallister–Hall
syndrome, gut mal rotation and gastric cancer.
HH signaling can promote the proliferation, metastasis, and drug resistance of
gastric cancer cells and inhibit their apoptosis
In gastritis, activation of HH signaling is required for the transformation of infiltrating
myeloid cells to myeloid-derived suppressor cells (MDSCs),
During Helicobacter pylori infection, the SHH ligand originating from gastric
parietal cells is ectopically expressed to induce metaplasia, which can eventually
lead to tumorigenesis
In GIC, the expression of SHH and IHH signaling pathway components and their target
genes is upregulated. Specifically, the expression of GLI1 is usually correlated with the
degree of malignancy of gastric cancer, especially with lymph node metastasis

14. Interaction between Hedgehog (HH) signaling and the tumor
microenvironment in gastrointestinal tumor cells

15. Conclusion
 Hh signaling is often aberrantly activated and plays an important role in the inflammation and
carcinogenesis of gastric epithelial cells.
 Abnormal HH signaling activation not only causes uncontrolled proliferation of tumor cells but
also contributes to the establishment of an immunosuppressive TME by regulating macrophage
and T cell-dependent immune responses as well as the expression of tumor-related inflammatory
factors.

16. References
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17. THANK YOU