在胰腺瘤和腺癌中,ROR2调节细胞可塑性
Simone Benitz1, Alec Steep2, Malak Nasser1
1Department of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
bioRxiv : the preprint server for biology
|January 3, 2024
概括
胰腺癌中的细胞可塑性涉及到细胞身份的转变. 受体氨酸激酶ROR2对胃细胞的认同产生对抗作用,促进瘤的进展,并影响胰腺管道腺癌 (PDAC) 的治疗反应.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞可塑性是胰腺管腺癌 (PDAC) 的关键特征,影响疾病进展和治疗结果.
- 正常的胰腺小细胞分化,由Pdx1调节,通常会抑制胃细胞的同一性.
- 这种胃细胞相同性在癌前病变和侵袭性PDAC亚型中观察到.
研究的目的:
- 研究受体氨酸激酶Ror2在胰腺癌进展期间调节细胞身份中的作用.
- 确定Ror2活动对PDAC攻击性和治疗反应的影响.
主要方法:
- 使用Ror2切除的胰腺瘤发生的小鼠模型.
- 分析了人类和小鼠胰腺癌组织的ROR2表达和细胞身份标记.
- 研究了ROR2对表皮细胞转化为介质细胞转化 (EMT) 和耐药性的影响.
主要成果:
- 确定Ror2作为胰腺胃代谢的标志物.
- 在小鼠模型中Ror2切除导致了在PDAC进展过程中持续的胃坑细胞身份.
- 在PDAC中,ROR2对抗胃坑细胞身份,促进EMT,赋予对KRAS抑制的抵抗力,并赋予对AKT抑制的脆弱性.
结论:
- 在PDAC发育和进展过程中,ROR2在调节细胞身份方面发挥着关键作用.
- 向ROR2可能通过调节细胞身份和克服治疗耐药性,为PDAC提供新的治疗策略.
- 了解ROR2,细胞身份和治疗反应之间的相互作用对于推进PDAC治疗至关重要.
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