期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 602, 期 -, 页码 84-90出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.02.038
关键词
Colorectal cancer; Neoadjuvant chemoradiation; FNDC1; PI3K/Akt; Stemness
资金
- National Natural Science Foundation of China [81773275, 81573004]
- Top-level Clinical Discipline Project of Shanghai Pudong [PWYgf2018-04]
- Pudong New District Health and Family Planning Commission Youth Science and Technology Project [PW2016B-4]
- Shanghai Health and Family Planning Commission Youth Science and Technology Project [202040303]
- Medical Science and Technology Project of Zhejiang Province [2020391513]
- Natural Science Foundation of Shanghai [21ZR1455900]
- Shanghai Municipal Health Commission [201940264]
- Shanghai Centre for Clinical Laboratory [2021ZXKT-01]
The aberrant expression of FNDC1 is associated with disease progression and poor prognosis in CRC. Upregulated FNDC1 predicts a poor response to nCRT, recurrence, and poor disease-free survival. FNDC1 also accelerates the stem cell-like properties of CRC cells.
Neoadjuvant chemoradiation (nCRT) followed by radical surgery is the preferred option for locally advanced colorectal cancer (CRC) treatment. However, chemo/radio-resistance remains a main obstacle in CRC therapy. In the study, we analyzed the mRNA expression profiling of CRC patients and revealed that the aberrant expression of fibronectin type III domain containing 1 (FNDC1) was associated with disease progression and poor prognosis in CRC. FNDC1 expression was consistently increased in multiple independent cohorts of CRC. Upregulated FNDC1 in pretreated primary tumor tissues predicted a poor response to nCRT, recurrence, and poor disease-free survival in nCRT-treated CRC patients. FNDC1 overexpression accelerated CRC cell survival on 5-FU or radiation treatment both in vitro and in vivo, whereas FNDC1 inhibition sensitized CRC cells to chemoradiation. In addition, FNDC1 accelerated stem cell-like properties of CRC cells. Furthermore, tumor tissues from non-responders exhibited higher activation of PI3K/Akt signaling than those from responders. FNDC1 depletion repressed 5-FU or irradiation-induced activation of PI3K/AKT in CRC cells. More importantly, pharmacological inhibition of PI3K/Akt signaling effectively decreased the effect of FNDC1 on chemoradiation resistance. Taken together, our study reveals the potential function of FNDC1 as a biomarker to predict nCRT sensitivity in CRC and a therapeutic target in CRC treatment. (C) 2022 The Authors. Published by Elsevier Inc.
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