Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma
Autor: | Ha-Yeon Shin, Joon-Yong Chung, Doo Byung Chay, Wookyeom Yang, Hyun Soo Kim, Jae Hoon Kim, Eun Ju Lee |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
0301 basic medicine endometriosis Cancer Research Tetraspanins Endometriosis AMP-Activated Protein Kinases Carcinoma Ovarian Epithelial Biology lcsh:RC254-282 Malignant transformation atypical endometriosis Young Adult 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Genetics medicine Humans Protein kinase A Research Articles Ovarian Neoplasms Cell growth General Medicine Middle Aged medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens AMP‐activated protein kinase 030104 developmental biology ovarian clear cell carcinoma Oncology tetraspanin 1 Gene Knockdown Techniques 030220 oncology & carcinogenesis Clear cell carcinoma Disease Progression Cancer research Molecular Medicine Female Atypical Endometriosis Ovarian cancer Research Article Adenocarcinoma Clear Cell |
Zdroj: | Molecular Oncology, Vol 15, Iss 4, Pp 987-1004 (2021) Molecular Oncology |
ISSN: | 1574-7891 1878-0261 |
Popis: | Ovarian clear cell carcinoma (OCCC) reportedly develops from endometriosis. However, the molecular mechanism underlying its malignant progression to OCCC remains elusive. This study aimed to identify an essential gene in the malignant transformation of endometriosis to OCCC. We performed RNA sequencing in formalin‐fixed, paraffin‐embedded (FFPE) tissues of endometriosis (n = 9), atypical endometriosis (AtyEm) (n = 18), adjacent endometriosis to OCCC (AdjEm) (n = 7), and OCCC (n = 17). We found that tetraspanin 1 (TSPAN1) mRNA level was significantly increased by 2.4‐ (DESeq2) and 3.4‐fold (edgeR) in AtyEm and by 80.7‐ (DESeq2) and 101‐fold (edgeR) in OCCC relative to endometriosis. We confirmed that TSPAN1 protein level was similarly overexpressed in OCCC tissues and cell lines. In immortalized endometriosis cell lines, TSPAN1 overexpression enhanced cell growth and invasion. Mechanistically, TSPAN1 triggered AMP‐activated protein kinase (AMPK) activity, promoting endometriosis and cell growth. Upregulated levels of TSPAN1 are considered an early event in the development of high‐risk endometriosis that could progress to ovarian cancer. Our study suggests the potential of TSPAN1 as a screening candidate for high‐risk endometriosis. Endometriosis can progress toward ovarian clear cell carcinoma (OCCC). While investigating genes involved in this process, we confirmed that TSPAN1 expression increases during progression from endometriosis to OCCC. TSPAN1 promoted endometriotic cell growth through AMPK activity. These results indicate altered TSPAN1 expression levels as an early marker of malignant transformation that may enable screening for high‐risk endometriosis. |
Databáze: | OpenAIRE |
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