LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer.
LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer.
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LRP 5促进结直肠癌中的癌症干细胞性状和化学抗性。
DOI：
10.1111/jcmm.17164
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发表时间：
2022-03
影响因子：
5.3
通讯作者：
Chen WD
中科院分区：
文献类型：
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作者：
Nie X;Liu H;Ye W;Wei X;Fan L;Ma H;Li L;Xue W;Qi W;Wang YD;Chen WD
经典Wnt/β-catenin通路的过度激活和癌症干细胞（cancer stem cells，CSC）的维持对于大多数人类癌症的发生和恶性进展至关重要。然而，它们在结直肠癌（CRC）中的调节机制尚未得到很好的证明。低密度脂蛋白受体相关蛋白5（LRP 5）已被确定为经典Wnt/β-catenin信号转导中与卷曲家族成员不可或缺的辅助受体。在本文中，我们表明LRP 5基因的激活通过激活经典的Wnt/β-catenin和IL-6/STAT 3信号通路促进CSC样表型，包括CRC细胞中的致瘤性和耐药性。临床上，LRP 5在人CRC组织中表达上调，并且与CRC患者的临床分期密切相关。进一步的分析表明，内源性LRP 5基因的沉默足以通过抑制这两条途径来抑制CRC的CSC样表型。综上所述，我们的研究结果不仅揭示了经典Wnt/β-catenin信号通路、IL-6/STAT 3信号通路和CD 133相关干细胞之间的调节性串扰促进了CRC的恶性行为，而且为CRC的诊断和治疗提供了有价值的靶点。
The overactivation of canonical Wnt/β‐catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low‐density lipoprotein receptor‐related protein 5 (LRP5) has been identified as an indispensable co‐receptor with frizzled family members for the canonical Wnt/β‐catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs‐like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/β‐catenin and IL‐6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs‐like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross‐talk between canonical Wnt/β‐catenin signalling pathway, IL‐6/STAT3 signalling pathway and CD133‐related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.
影响因子：
5
作者：
Horne, Logan;Avilucea, Frank R.;Jin, Huifeng;Barrott, Jared J.;Smith-Fry, Kyllie;Wang, Yanliang;Hoang, Bang H.;Jones, Kevin B.
通讯作者：
Jones, Kevin B.