High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast.
10.1007/s11684-023-1009-7
- Author:
Dawei XIE
1
;
Zheng WANG
1
;
Beibei SUN
1
;
Liwei QU
2
;
Musheng ZENG
3
;
Lin FENG
4
;
Mingzhou GUO
5
;
Guizhen WANG
6
;
Jihui HAO
7
;
Guangbiao ZHOU
8
Author Information
1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
2. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing, 100101, China.
3. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
4. Department of Gastroenterology & Hepatology and Department of Pathology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
5. Department of Gastroenterology & Hepatology and Department of Pathology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China. mzguo@hotmail.com.
6. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gzwang@cicams.ac.cn.
7. Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. haojihui@tjmuch.com.
8. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gbzhou@cicams.ac.cn.
- Publication Type:Journal Article
- Keywords:
FAK 6/7;
SRRM4;
breast;
neuroendocrine neoplasms;
pancreas
- MeSH:
Female;
Humans;
Alternative Splicing;
Breast Neoplasms/metabolism*;
Carcinoma, Pancreatic Ductal/pathology*;
Focal Adhesion Protein-Tyrosine Kinases/therapeutic use*;
Nerve Tissue Proteins/genetics*;
Neuroendocrine Tumors/genetics*;
Oncogenes;
Pancreatic Neoplasms/metabolism*
- From:
Frontiers of Medicine
2023;17(5):907-923
- CountryChina
- Language:English
-
Abstract:
The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
