Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma

Ha Yeon Shin; Wookyeom Yang; Doo Byung Chay; Eun ju Lee; Joon Yong Chung; Hyun Soo Kim; Jae Hoon Kim

doi:10.1002/1878-0261.12884

Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma

Ha Yeon Shin, Wookyeom Yang, Doo Byung Chay, Eun ju Lee, Joon Yong Chung, Hyun Soo Kim, Jae Hoon Kim

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Abstract

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.

Original language	English
Pages (from-to)	987-1004
Number of pages	18
Journal	Molecular Oncology
Volume	15
Issue number	4
DOIs	https://doi.org/10.1002/1878-0261.12884
Publication status	Published - 2021 Apr

Bibliographical note

Funding Information:
Paraffin blocks were provided by the Korea Gynecologic Cancer Bank through Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF‐2017M3A9B8069610), and were obtained from the Human Tissue Bank of Gangnam Severance Hospital, Yonsei University College of Medicine. The study was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2015R1D1A1A01059335, NRF‐2017R1D1A1A09000576, NRF‐2017R1A2B2008505, and NRF‐2019R1A6A3A13092928).

Funding Information:
This study was approved by the Institutional Review Board of Gangnam Severance Hospital (3‐2015‐0298; Seoul, Republic of Korea). The experiments were undertaken with each patient's understanding and written consent, which was following the Declaration of Helsinki. All formalin‐fixed, paraffin‐embedded tissue samples were provided by the Korea Gynaecologic Cancer Bank through the Bio & Medical Technology Development Program of the Korean Ministry of Education, Science and Technology. For RNA sequencing, the FFPE tissue blocks comprised endometriosis ( = 9), AtyEm ( = 18), adjacent endometriosis to OCCC (AdjEm) ( = 7), OCCC ( = 17), and ovarian endometrioid carcinoma (OEC) ( = 12). For tissue microarray (TMA), the FFPE tissue blocks comprised endometriosis ( = 83), AtyEm ( = 13), AdjEm ( = 4), OCCC ( = 51), and OEC ( = 53). n n n n n n n n n n

Publisher Copyright:
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/1878-0261.12884

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title = "Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma",

abstract = "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.",

author = "Shin, {Ha Yeon} and Wookyeom Yang and Chay, {Doo Byung} and Lee, {Eun ju} and Chung, {Joon Yong} and Kim, {Hyun Soo} and Kim, {Jae Hoon}",

note = "Funding Information: Paraffin blocks were provided by the Korea Gynecologic Cancer Bank through Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF‐2017M3A9B8069610), and were obtained from the Human Tissue Bank of Gangnam Severance Hospital, Yonsei University College of Medicine. The study was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2015R1D1A1A01059335, NRF‐2017R1D1A1A09000576, NRF‐2017R1A2B2008505, and NRF‐2019R1A6A3A13092928). Funding Information: This study was approved by the Institutional Review Board of Gangnam Severance Hospital (3‐2015‐0298; Seoul, Republic of Korea). The experiments were undertaken with each patient's understanding and written consent, which was following the Declaration of Helsinki. All formalin‐fixed, paraffin‐embedded tissue samples were provided by the Korea Gynaecologic Cancer Bank through the Bio & Medical Technology Development Program of the Korean Ministry of Education, Science and Technology. For RNA sequencing, the FFPE tissue blocks comprised endometriosis ( = 9), AtyEm ( = 18), adjacent endometriosis to OCCC (AdjEm) ( = 7), OCCC ( = 17), and ovarian endometrioid carcinoma (OEC) ( = 12). For tissue microarray (TMA), the FFPE tissue blocks comprised endometriosis ( = 83), AtyEm ( = 13), AdjEm ( = 4), OCCC ( = 51), and OEC ( = 53). n n n n n n n n n n Publisher Copyright: {\textcopyright} 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.",

year = "2021",

month = apr,

doi = "10.1002/1878-0261.12884",

language = "English",

volume = "15",

pages = "987--1004",

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AU - Shin, Ha Yeon

AU - Yang, Wookyeom

AU - Chay, Doo Byung

AU - Lee, Eun ju

AU - Chung, Joon Yong

AU - Kim, Hyun Soo

AU - Kim, Jae Hoon

N1 - Funding Information: Paraffin blocks were provided by the Korea Gynecologic Cancer Bank through Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF‐2017M3A9B8069610), and were obtained from the Human Tissue Bank of Gangnam Severance Hospital, Yonsei University College of Medicine. The study was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2015R1D1A1A01059335, NRF‐2017R1D1A1A09000576, NRF‐2017R1A2B2008505, and NRF‐2019R1A6A3A13092928). Funding Information: This study was approved by the Institutional Review Board of Gangnam Severance Hospital (3‐2015‐0298; Seoul, Republic of Korea). The experiments were undertaken with each patient's understanding and written consent, which was following the Declaration of Helsinki. All formalin‐fixed, paraffin‐embedded tissue samples were provided by the Korea Gynaecologic Cancer Bank through the Bio & Medical Technology Development Program of the Korean Ministry of Education, Science and Technology. For RNA sequencing, the FFPE tissue blocks comprised endometriosis ( = 9), AtyEm ( = 18), adjacent endometriosis to OCCC (AdjEm) ( = 7), OCCC ( = 17), and ovarian endometrioid carcinoma (OEC) ( = 12). For tissue microarray (TMA), the FFPE tissue blocks comprised endometriosis ( = 83), AtyEm ( = 13), AdjEm ( = 4), OCCC ( = 51), and OEC ( = 53). n n n n n n n n n n Publisher Copyright: © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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Y1 - 2021/4

N2 - 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.

AB - 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.

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Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma

Abstract

Bibliographical note

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