Related Experiment Video
Updated: May 8, 2026
Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
Expression of GLTSCR2/Pict-1 in squamous cell carcinomas of the skin
Jee-Youn Kim1, Young-Eun Cho, Jae-Hoon Park
1Department of Pathology, School of Medicine, Kyung Hee University, Seoul, 130-701, Korea.
Abstract:
The most important cause of cutaneous squamous cell carcinomas (SCC) is DNA damage induced by exposure to solar UV irradiation. DNA damage induced by UV irradiation is sensed by early DNA damage response (DDR) proteins. Recently, GLTSCR2 has been suggested to play a role in UV light-induced DDR. To explore the role of GLTSCR2 in the development of cutaneous SCC, we investigated the molecular mechanism underlying GLTSCR2 inactivation in response to UV irradiation. We analyzed cutaneous SCC (n=42), basal cell carcinomas (BCC; n=26), and normal skin tissue samples (n=36) and compared GLTSCR2 expression between tumor and normal tissues, using immunohistochemistry. Next, to investigate the effects of UV irradiation on GLTSCR2, we performed immunocytochemistry, RT-PCR, immunoblotting, half-life assay for GLTSCR2, and comet assay after UV irradiation in primary keratinocytes. GLTSCR2 expression in SCC was significantly lower than that of normal skin tissue (p<0.05), but not different between BCC and normal skin. In cultured primary keratinocytes, GLTSCR2 expression was decreased and translocated after UV irradiation. UV irradiation accelerated degradation of GLTSCR2 through proteasomal pathway. Knockdown of GLTSCR2 resulted in marked decrease in γH2AX foci after UV exposure. Furthermore, comet assay showed that DNA damage after UV exposure persists longer in GLTSCR2 knocked-down cells. Our data show that GLTSCR2 is downregulated in SCC of the skin and that UV light exposure decreases the stability of GLTSCR2 and sensitizes keratinocytes to DNA damage. Therefore, our data suggest that GLTSCR2 might be involved in the development and/or progression of SCC of the skin.
Insights
The protein GLTSCR2 is reduced in skin squamous cell carcinoma (SCC) and becomes unstable after UV exposure, increasing DNA damage and potentially contributing to SCC development.
Area of Science:
- Dermatology
- Molecular Biology
- Cancer Research
Background:
- Cutaneous squamous cell carcinoma (SCC) is primarily caused by UV-induced DNA damage.
- The DNA damage response (DDR) pathway involves proteins that sense and repair DNA lesions.
- GLTSCR2 is a recently identified protein implicated in the UV-induced DDR.
Purpose of the Study:
- To investigate the role of GLTSCR2 in the development of cutaneous SCC.
- To elucidate the molecular mechanisms of GLTSCR2 inactivation following UV irradiation.
Main Methods:
- Immunohistochemistry on human skin tissues (SCC, BCC, normal).
- UV irradiation experiments on primary keratinocytes.
- Assays included immunocytochemistry, RT-PCR, immunoblotting, half-life assay, and comet assay.
- GLTSCR2 knockdown was performed to assess its functional impact.
Main Results:
- GLTSCR2 expression was significantly lower in SCC compared to normal skin.
- UV irradiation decreased GLTSCR2 expression and accelerated its proteasomal degradation in keratinocytes.
- GLTSCR2 knockdown led to reduced DNA repair (fewer γH2AX foci) and persistent DNA damage after UV exposure.
- GLTSCR2 levels were not different between basal cell carcinoma (BCC) and normal skin.
Conclusions:
- GLTSCR2 is downregulated in skin SCC and its stability is compromised by UV light.
- UV-induced GLTSCR2 instability sensitizes keratinocytes to DNA damage.
- GLTSCR2 may play a role in the pathogenesis and progression of cutaneous SCC.
