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
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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