SERTAD1 Sensitizes Breast Cancer Cells to Doxorubicin and Promotes Lysosomal Protein Biosynthesis

Biomedicines

Hye-gyeong Lee¹  Davaajargal Myagmarjav¹  Beom Suk Lee¹  Son Hai Vu¹  Yeongseon Choi¹  Taeyeon Jo¹  Samil Jung¹  Hyojeong Lee¹  Hai Anh Nguyen¹  Thi Ngoc Quynh Nguyen¹  Myeong-Sok Lee¹ 

[1] Department of Biological Science, Sookmyung Women’s University, Seoul 04310, Korea;

关键词: breast cancer;    anti-cancer drugs;    anoikis;    autophagy;    SERTAD1;    lysosomal biogenesis;   

DOI  :  10.3390/biomedicines10051148

来源: DOAJ

【 摘 要 】

Acquired chemoresistance of tumor cells is an unwanted consequence of cancer treatment. Overcoming chemoresistance is particularly important for efficiently improving cancer therapies. Here, using multiple lines of evidence, we report the suppressive role of SERTAD1 in apoptosis/anoikis. Among various breast cancer cell lines, higher SERTAD1 expression was found in MCF7 and MDA-MB-231 in suspension than in adherent cell culture. We revealed an unexpected phenomenon that different types of cell deaths were induced in response to different doses of doxorubicin (Dox) in breast cancer cells, presumably via lysosomal membrane permeabilization. A low dose of Dox highly activated autophagy, while a high dose of the chemotherapy induced apoptosis. Inhibition of SERTAD1 promoted the sensitivity of breast cancer cells to Dox and paclitaxel, leading to a significant reduction in tumor volumes of xenograft mice. Simultaneously targeting cancer cells with Dox and autophagy inhibition successfully induced higher apoptosis/anoikis. The novel role of SERTAD1 in maintaining cellular homeostasis has also been suggested in which lysosomal contents, including LAMP1, LAMP2, CTSB, and CTSD, were reduced in SERTAD1-deficient cells.

【 授权许可】

Unknown