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Decreased TMEM40 expression is associated with malignant behavior of cutaneous squamous cell carcinoma and inhibits
Lei Yu1, Jie Liu2, Tang-De Zhang1
1Department of Dermatology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
Abstract:
Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer in humans worldwide. The identification and characterization of cancer-associated transmembrane proteins are important for understanding the molecular biology of CSCC. The aim of the present study was to evaluate the expression pattern of transmembrane protein 40 (TMEM40) in CSCC and its clinical significance. The underlying mechanisms were also examined. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analysis were used to determine the relative expression of TMEM40 in CSCC cell lines and clinical tissue samples. The effect of TMEM40 gene silencing on cell proliferation was also evaluated using Cell Counting Kit-8 assays. Wound healing assays, flow cytometry and Transwell assays were used to explore the migration, cell cycle distribution/apoptosis and invasion of CSCC cells following TMEM40 silencing, respectively. In the present study, increased TMEM40 expression was observed in CSCC tissue samples, compared with normal skin, and TMEM40 expression was associated with large tumor size in patients with CSCC. In vitro functional assays indicated that TMEM40 was involved in the regulation of A431 and SCL1 cell growth through its effects on the cell cycle and apoptosis. Silencing TMEM40 in A431 and SCL1 cells resulted in cell cycle arrest at the G0/G1 phase and promoted apoptosis. In addition, migration and invasion were significantly inhibited following silencing of TMEM40 expression in CSCC cells. Taken together, the results of the present study indicated that reduced TMEM40 expression could inhibit CSCC development and that TMEM40 may represent a therapeutic target in CSCC.
Insights
Transmembrane protein 40 (TMEM40) is elevated in cutaneous squamous cell carcinoma (CSCC). Reducing TMEM40 inhibits CSCC cell growth, migration, and invasion, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (CSCC) is a prevalent human skin cancer.
- Understanding cancer-associated transmembrane proteins is crucial for CSCC molecular biology.
- Transmembrane protein 40 (TMEM40) role in CSCC requires investigation.
Purpose of the Study:
- To evaluate TMEM40 expression patterns in CSCC.
- To determine the clinical significance of TMEM40 in CSCC.
- To elucidate the underlying mechanisms of TMEM40 in CSCC progression.
Main Methods:
- Quantitative PCR, Western blot, and immunohistochemistry for TMEM40 expression analysis.
- Cell Counting Kit-8 assays for proliferation assessment.
- Wound healing, flow cytometry, and Transwell assays for migration, cell cycle, apoptosis, and invasion studies.
Main Results:
- TMEM40 expression is significantly increased in CSCC tissues compared to normal skin.
- Elevated TMEM40 expression correlates with larger tumor size in CSCC patients.
- TMEM40 silencing in CSCC cells induced G0/G1 cell cycle arrest, promoted apoptosis, and inhibited migration and invasion.
Conclusions:
- TMEM40 plays a role in regulating CSCC cell growth, cell cycle, apoptosis, migration, and invasion.
- Reduced TMEM40 expression inhibits CSCC development.
- TMEM40 represents a potential therapeutic target for CSCC treatment.
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