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Updated: Aug 9, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Somatostatin receptor 4 (SSTR4) is a tumor suppressor in cutaneous and head & neck squamous cell carcinomas
Ali Taqvi1,2, Tuan Khang Huynh1,2, Adway Kadam2,3
1Division of Clinical and Translational Research, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Abstract:
The mutational landscape of head & neck and cutaneous squamous cell carcinomas (HNSCC, cSCC) has major gene alterations involving PIK3CA, NOTCH1, and TP53 among others that contribute to tumorigenesis. In this study, we focused on somatostatin receptor 4 (SSTR4), which was identified in a recent in vivo HNSCC CRISPR screen. Mutations in the SSTR protein family are more commonly implicated in neuroendocrine tumors, and to date, no studies have shown a link between SSTR4 and cSCC/HNSCC. To understand the role of Sstr4 in skin keratinocytes, we employed transcriptomic profiling and proteomic methods and identified enriched pathways and protein-protein interactions (PPIs) networks. Sstr4 activation by J-2156 agonist regulated MAPK-ERK signaling pathway, which simultaneously limited G1 to S phase cell cycle progression. To validate Sstr4 as a driver of cSCC/HNSCC tumorigenesis, we performed a localized and clonal Sstr4 knockout in basal keratinocytes of the Pik3caH1047R oncogenic mouse model using ultrasound-guided in-utero lentivirus injection technology. Tumor formation in mice following Sstr4 knockout occurred rapidly around 12 weeks. Our study is the first to uncover Sstr4 role in cSCC/HNSCC through in-vivo models.
Insights
Somatostatin receptor 4 (SSTR4) plays a novel role in skin cancer development. SSTR4 activation limits cell cycle progression, and its knockout accelerates tumor formation in mice, revealing its potential as a therapeutic target for head & neck and cutaneous squamous cell carcinomas.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Head & neck and cutaneous squamous cell carcinomas (HNSCC, cSCC) exhibit complex mutational landscapes involving PIK3CA, NOTCH1, and TP53.
- Somatostatin receptor family mutations are typically linked to neuroendocrine tumors, with no prior evidence connecting SSTR4 to HNSCC or cSCC.
Purpose of the Study:
- To investigate the role of somatostatin receptor 4 (SSTR4) in skin keratinocytes and its potential involvement in HNSCC/cSCC tumorigenesis.
- To explore SSTR4's functional pathways and its impact on cell cycle regulation.
Main Methods:
- Transcriptomic profiling and proteomic analysis to identify SSTR4-associated pathways and protein-protein interactions (PPIs).
- Utilized a J-2156 agonist to activate SSTR4 and assess its effect on the MAPK-ERK signaling pathway and cell cycle.
- Generated a localized, clonal Sstr4 knockout in basal keratinocytes of a Pik3caH1047R mouse model using ultrasound-guided in-utero lentivirus injection.
Main Results:
- Sstr4 activation by J-2156 modulated the MAPK-ERK signaling pathway, inhibiting G1 to S phase cell cycle progression.
- Sstr4 knockout in the mouse model led to rapid tumor formation by 12 weeks.
- This study provides the first in-vivo evidence of SSTR4's role in HNSCC and cSCC development.
Conclusions:
- SSTR4 is implicated in the tumorigenesis of HNSCC and cSCC.
- The findings highlight SSTR4 as a potential therapeutic target for these skin cancers.
- Further research into SSTR4 signaling pathways may uncover novel treatment strategies.
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