GIST, 난치성 항암치료 효능 극대화 새로운 치료전략 제시 Aberrant activation of the CD45-Wnt signaling axis promotes stemness and therapy resistance in colorectal cancer cells

출처 : Theranostics
등록일 : 2021-09-06
조회 : 58

<div style="text-align: justify;" align="justify"><span style="font-family: 돋움, dotum; font-size: 11pt; color: rgb(58, 50, 195);"><span style="color: rgb(0, 0, 0); font-size: 11pt; font-family: 돋움, dotum;"></span></span><span style="color: rgb(0, 0, 0); font-size: 11pt; font-family: 돋움, dotum;">👉 논문명:&nbsp; </span><a href="https://www.thno.org/v11p8755" target="_blank"><span style="color: rgb(0, 0, 0); font-size: 11pt; font-family: 돋움, dotum;">Aberrant activation of the CD45-Wnt signaling axis promotes stemness and therapy resistance in colorectal cancer cells(Theranostics, 2021.09.06)</span></a></div><div style="text-align: justify;" align="justify"><br></div><div style="text-align: justify;" align="justify"><span style="font-family: 돋움, dotum; font-size: 11pt; color: rgb(58, 50, 195);"><b><br></b></span></div><div style="text-align: justify;" align="justify"><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Abstract</b></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b><br></b></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Rationale:</b> Chemoradiation (CRT) is commonly used as an adjuvant or neoadjuvant treatment for colorectal cancer (CRC) patients. However, resistant cells manage to survive and propagate after CRT, increasing the risk of recurrence. Thus, better understanding the mechanism of resistant cancer cells is required to achieve better clinical outcomes.</span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 14.6667px;"><br></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Methods:</b> Here, we explored gene expression profiling of CRC patient tumors to identify therapy resistance genes and discovered that protein tyrosine phosphatase receptor type C (PTPRC), which encodes CD45, was increased in remnant tumor tissues after CRT and correlated with metastasis. Through multiple validations using patient tumors and CRC cell lines, we found for the first time the increase of CD45 expression in CRC (EpCAM+) epithelial cells surviving after CRT. Thus, we investigated the biological role and downstream events of CD45 were explored in human CRC cells and CRC mouse models.</span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 14.6667px;"><b><br></b></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Results:</b> Increased CD45 expression in cancer cells in pretreated primary tumors accounts for poor regression and recurrence-free survival in CRT-treated patients. High CD45 expression promotes CRC cell survival upon 5-fluorouracil or radiation treatment, while CD45 depletion sensitizes CRC cells to CRT. Intriguingly, CD45 is preferentially expressed in cancer stem-like cells (CSCs), as determined by spheroid culture and the expression of CSC markers, and is required for the distinct functions of CSCs, such as cancer initiation, repopulation, and metastasis. Mechanistically, CD45 phosphatase activity promotes Wnt transcriptional activity by stabilizing the β-catenin protein, which collectively enhances stemness and the therapy-resistant phenotype.</span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 14.6667px;"><br></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Conclusions:</b> Our results highlight a novel function of CD45 as a mediator of CRT resistance and provide a potential therapy strategy for CRC therapy.</span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 14.6667px;"><br></span></font></div><div align="justify" style="text-align: justify;"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;"><b>Keywords:</b> Chemoradiation, Colorectal cancer, Therapy resistance, CD45, Cancer stem-like cell, Wnt, β-Catenin</span></font></div></div><div style="text-align: justify;" align="justify"><span style="font-family: 돋움, dotum; font-size: 11pt; color: rgb(58, 50, 195);"><br></span></div><div style="text-align: justify;" align="justify"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;">👉 논문보러가기:&nbsp;<a href="https://www.thno.org/v11p8755" target="_blank"><span style="font-size: 11pt; color: rgb(0, 0, 0); font-family: 돋움, dotum;">https://www.thno.org/v11p8755</span></a></span></font></div><div style="text-align: justify;" align="justify"><font color="#3a32c3" face="돋움, dotum"><span style="font-size: 14.6667px;"><br></span></font></div><div style="text-align: justify;" align="justify"><span style="font-family: 돋움, dotum; font-size: 11pt; color: rgb(58, 50, 246);">※ 자세한 내용은 URL을 확인하시기 바랍니다.</span></div>

URL : https://www.thno.org/v11p8755

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