PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy.
Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics.
Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
Ji-Hoon
JH
Park
Department of Life Science, Chung-Ang University, South Korea.
Keun Pil
KP
Kim
Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
Jeong-Jae
JJ
Ko
Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea. Electronic address: kspark@cha.ac.kr.
Kyung-Soon
KS
Park
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms
D000903:Antibiotics, Antineoplastic; C527883:Elk3 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D004317:Doxorubicin; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
Autophagy; Doxorubicin; ELK3; MDA-MB-231 cell line; PI3K/Akt