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Open AccessArticle

Impact of FAK Expression on the Cytotoxic Effects of CIK Therapy in Triple-Negative Breast Cancer

by Mei-Ren Pan 1,2,†, Cheng-Che Wu 3,4,†, Jung-Yu Kan 3,4, Qiao-Lin Li 1, Shu-Jyuan Chang 5, Chun-Chieh Wu 2,6, Chung-Liang Li 3,4, Fu Ou-Yang 2,3,4, Ming-Feng Hou 1,2,3,4,5, Hon-Kan Yip 7,8 and Chi-Wen Luo 2,3,4,*
1
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
2
Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
3
Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
4
Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
5
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
6
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
7
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
8
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(1), 94; https://doi.org/10.3390/cancers12010094
Received: 15 November 2019 / Revised: 12 December 2019 / Accepted: 27 December 2019 / Published: 30 December 2019
Triple-negative breast cancer (TNBC) is a special subtype of breast cancer in which several common diagnostic biomarkers are lost. Due to the loss of expression of receptors, treatment options for TNBC are limited. Therefore, finding safe and effective treatments for patients with TNBC is a major objective for clinicians. Previous studies suggested that cytokine-induced killer (CIK) cells may be beneficial for patients with a variety of tumor types. However, CIK therapy is not effective for all patients. In this study, we found that focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase that regulates several cellular functions in different cells, has the potential to regulate tumor cells sensitized to CIK cells. Knockdown of FAK expression in TNBC cells or the treatment of TNBC cells with a FAK inhibitor followed by coculture with CIK cells increases death of TNBC cells, suggesting that FAK plays important roles in sensitizing tumor cells to CIK cells. This phenomenon could be regulated by a FAK-programmed death-ligand 1 (PD-L1)-related mechanism. Overall, our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment, and show that CIK cell therapy combined with FAK inhibitors may be a novel therapeutic strategy for patients with TNBC. View Full-Text
Keywords: cytokine induced killer cells (CIK); focal adhesion kinase (FAK); apoptosis; cytotoxicity; programmed death-ligand 1 (PD-L1); triple-negative breast cancer (TNBC) cytokine induced killer cells (CIK); focal adhesion kinase (FAK); apoptosis; cytotoxicity; programmed death-ligand 1 (PD-L1); triple-negative breast cancer (TNBC)
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Pan, M.-R.; Wu, C.-C.; Kan, J.-Y.; Li, Q.-L.; Chang, S.-J.; Wu, C.-C.; Li, C.-L.; Ou-Yang, F.; Hou, M.-F.; Yip, H.-K.; Luo, C.-W. Impact of FAK Expression on the Cytotoxic Effects of CIK Therapy in Triple-Negative Breast Cancer. Cancers 2020, 12, 94.

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