PMID- 38284248
OWN - NLM
STAT- Publisher
LR  - 20240201
IS  - 1699-5848 (Electronic)
IS  - 0213-3911 (Linking)
DP  - 2024 Jan 8
TI  - Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring 
      BRAF(V600E) to Vemurafenib by Bim upregulation.
PG  - 18705
LID - 10.14670/HH-18-705 [doi]
AB  - Pseudopodium-enriched atypical kinase 1 (PEAK1) has been demonstrated to be 
      upregulated in human malignancies and cells. Enhanced PEAK1 expression 
      facilitates tumor cell survival and chemoresistance. However, the role of PEAK1 
      inhibition to anaplastic thyroid carcinoma cell (ATC) and vemurafenib resistance 
      is still unknown. Here, we observed that targeting PEAK1 inhibited cell viability 
      and colony formation, but not cell apoptosis in both of the 8505C and Hth74 cells 
      in vitro. Targeting PEAK1 sensitized 8505C and Hth74 cells to vemurafenib by 
      inducing cell apoptosis, and thereby decreasing cell viability. Mechanistically, 
      vemurafenib treatment upregulated PEAK1 expression. Combined PEAK1 depletion and 
      Vemurafenib treatment upregulated Bim expression. Targeting PEAK1 sensitized 
      vemurafenib-induced apoptosis by upregulating Bim. In conclusion, vemurafenib 
      resistance in ATC cells harboring BRAF(V600E) is associated with PEAK1 
      activation, resulting in the inhibition of pro-apoptotic Bim protein. Therefore, 
      targeting PEAK1 may be an effective strategy to sensitize ATC harboring 
      BRAF(V600E) to vemurafenib.
CI  - (c)The Author(s) 2024. Open Access. This article is licensed under a Creative 
      Commons CC-BY International License.
FAU - Wang, Qiuhan
AU  - Wang Q
AD  - Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, PR China.
FAU - Hao, Fengyun
AU  - Hao F
AD  - Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, PR China. haofengyun5166209@qdu.edu.cn.
FAU - Ning, Liang
AU  - Ning L
AD  - Department of Thyroid Surgery, the Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, PR China.
FAU - Sun, Chong
AU  - Sun C
AD  - Department of Spine Surgery, the Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, PR China. sunchongjz@qduhospital.cn.
LA  - eng
GR  - 2021026/Youth Scientific Research Fund of Qingdao University/
PT  - Journal Article
DEP - 20240108
PL  - Spain
TA  - Histol Histopathol
JT  - Histology and histopathology
JID - 8609357
SB  - IM
EDAT- 2024/01/29 06:44
MHDA- 2024/01/29 06:44
CRDT- 2024/01/29 05:29
PHST- 2024/01/29 06:44 [pubmed]
PHST- 2024/01/29 06:44 [medline]
PHST- 2024/01/29 05:29 [entrez]
AID - HH-18-705 [pii]
AID - 10.14670/HH-18-705 [doi]
PST - aheadofprint
SO  - Histol Histopathol. 2024 Jan 8:18705. doi: 10.14670/HH-18-705.