학술논문
GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways
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- 영문명
- GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways
- 발행기관
- 대한생리학회-대한약리학회
- 저자명
- Gang Wang Baisha Ouyang Fang Jing Xiaoyan Dai
- 간행물 정보
- 『The Korean Journal of Physiology & Pharmacology』제27권 제1호, 21~29쪽, 전체 9쪽
- 주제분류
- 의약학 > 의학일반
- 파일형태
- 발행일자
- 2023.01.31
4,000원
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국문 초록
영문 초록
The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof- function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin’s efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin’s efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.
목차
INTRODUCTION
METHODS
RESULTS
DISCUSSION
FUNDING
ACKNOWLEDGEMENTS
CONFLICTS OF INTEREST
SUPPLEMENTARY MATERIALS
REFERENCES
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