Back to Search
Start Over
Up-regulated FNDC1 accelerates stemness and chemoradiation resistance in colorectal cancer cells.
- Source :
-
Biochemical & Biophysical Research Communications . Apr2022, Vol. 602, p84-90. 7p. - Publication Year :
- 2022
-
Abstract
- 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. • FNDC1 expression was increased in CRC patient. • Upregulated FNDC1 predicted a poor response to nCRT. • FNDC1 accelerated CRC cell survival on 5-FU or radiation treatment. • FNDC1 accelerated stem cell-like properties of CRC cells. • FNDC1 depletion repressed 5-FU or irradiation-induced PI3K/AKT activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 602
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 155861475
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.02.038