The role of α-actinin-4 in regulation of cancer cell stemness in cervical cancer
- 주제(키워드) cancer stem cell , cervical cancer , α-actinin-4
- 발행기관 고려대학교 대학원
- 지도교수 고제상
- 발행년도 2018
- 학위수여년월 2018. 2
- 학위구분 석사
- 학과 대학원 생명과학과
- 세부전공 세포생물학 전공
- 원문페이지 49 p
- 실제URI http://www.dcollection.net/handler/korea/000000080370
- 본문언어 영어
- 제출원본 000045932333
초록/요약
Cancer stem cells (CSCs) can initiate tumors and possess the properties of self-renewal and differentiation. Since CSCs are responsible for chemoresistance, CSCs are known as a key factor of cancer recurrence. α-actinin-4 (ACTN4) is an actin-binding protein, which is involved in muscle differentiation and cancer metastasis. ACTN4 promotes the epithelial to mesenchymal transition and cell cycle through β-catenin stabilization in cervical cancer. In this study, I investigated whether ACTN4 is involved in regulation of CSC population and cancer progression in cervical cancer. Results from gene expression database analysis showed that the mRNA expression of ACTN4 was elevated in cancerous cervix, compared to normal cervix. Knockdown of ACTN4 suppressed formation of CSCs. ACTN4 knockdown cells exhibited a decreased CSC size and CD44+/CD24- population. ACTN4 knockdown also inhibited proliferation of CSCs and was sensitive to anti-cancer drugs by downregulating ABCG2, which plays a role in drug resistance. These findings suggest that ACTN4 promotes cancer stem cell properties and contributes to drug resistance in cervical cancer.
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CONTENTS
LIST OF TABLE
LIST OF FIGURES
ABBREVIATIONS
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
Materials
Cell culture and generation of stable cell lines
Sphere formation assay
Flow cytometric analysis
Aldehyde dehydrogenase activity assay
Western blot analysis
RNA isolation and real-time PCR
Cell proliferation assay
3D culture and immunofluorescence imaging
Differentiation assay
Cytotoxicity assay
Statistical analysis
RESULTS
Knockdown of ACTN4 suppresses formation of CSCs in cervical cancer cells
ACTN4 regulates expressions of CSC markers in cervical cancer cells
Knockdown of ACTN4 inhibits proliferation of CSCs and decreases EMT
ACTN4 knockdown cells are more susceptible to anti-cancer drugs than normal cells
DISCUSSION
REFERENCES
ABSTRACT IN KOREAN
