PMID- 31853379 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1976-8354 (Print) IS - 2151-2485 (Electronic) IS - 1976-8354 (Linking) VI - 23 IP - 6 DP - 2019 TI - Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway. PG - 414-421 LID - 10.1080/19768354.2019.1666030 [doi] AB - Certain cancer types, including breast cancer, are accompanied with stiffening of the surrounding extracellular matrix (ECM). Previous studies suggest that this stiffened matrix influences cancer cell progression, such as proliferation and invasion, both biochemically and mechanically. However, the contribution of ECM stiffness to cellular response to diverse stresses, which most cancer cells are exposed to, has not been elucidated. In this study, we demonstrate that expression of the Shwachman-Bodian-Diamond syndrome protein (SDBS) in a stiff matrix protects cells from apoptosis induced by environmental stress, including anticancer drugs. Cells cultured on stiff matrices were less apoptotic process induced by serum depletion than those cultured on the soft matrix. Interestingly, knockdown (KD) of SDBS among the apoptosis-related genes significantly increased apoptosis induced by serum depletion in cells cultured in a stiff matrix. Apoptosis of SDBS KD cells in a stiff matrix was significantly inhibited by the caspase 8 inhibitor, indicating that activation of the caspase 8 pathway by SDBS KD is critical for cancer cell apoptosis in stiff matrices. Additionally, we also found that downregulation of SDBS also effectively increased cell death induced by anticancer drugs, including paclitaxel, cisplatin, and eribulin. Taken together, our findings suggest that inhibition of SDBS enhances effective chemotherapy of malignant breast cancer cells in stiff ECM environments. CI - (c) 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. FAU - Lee, Jieun AU - Lee J AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Ko, Panseon AU - Ko P AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - You, Eunae AU - You E AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Jeong, Jangho AU - Jeong J AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Keum, Seula AU - Keum S AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Kim, Jaegu AU - Kim J AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Rahman, Mizanur AU - Rahman M AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Lee, Dong Ho AU - Lee DH AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. FAU - Rhee, Sangmyung AU - Rhee S AD - Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea. LA - eng PT - Journal Article DEP - 20190920 PL - England TA - Anim Cells Syst (Seoul) JT - Animal cells and systems JID - 101478641 PMC - PMC6913620 OTO - NOTNLM OT - ECM stiffness OT - SBDS OT - apoptosis OT - breast cancer OT - caspase EDAT- 2019/12/20 06:00 MHDA- 2019/12/20 06:01 PMCR- 2019/09/20 CRDT- 2019/12/20 06:00 PHST- 2019/08/07 00:00 [received] PHST- 2019/08/25 00:00 [revised] PHST- 2019/08/26 00:00 [accepted] PHST- 2019/12/20 06:00 [entrez] PHST- 2019/12/20 06:00 [pubmed] PHST- 2019/12/20 06:01 [medline] PHST- 2019/09/20 00:00 [pmc-release] AID - 1666030 [pii] AID - 10.1080/19768354.2019.1666030 [doi] PST - epublish SO - Anim Cells Syst (Seoul). 2019 Sep 20;23(6):414-421. doi: 10.1080/19768354.2019.1666030. eCollection 2019.