Perelli Luigi, Genovese Giannicola
Department of Genitourinary Medical Oncology.
TRACTION platform, and.
J Clin Invest. 2025 Jun 2;135(11). doi: 10.1172/JCI193205.
Cell plasticity is a hallmark of cancer, enabling tumor cells to acquire multiple phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this issue of the JCI, Kawai and colleagues leveraged genetically engineered mouse models (GEMM) of pancreatic ductal adenocarcinoma (PDAC) to demonstrate that loss of Pbrm1, a member of the SWI/SNF complex, drives dedifferentiation and aggressive tumor features. Pbrm1 loss activated a program of epithelial-to-mesenchymal transition (EMT) and allowed the emergence of poorly differentiated histologies that are commonly associated with high recurrence rate and dismal prognosis. These findings reveal the role of the SWI/SNF complex during PDAC evolution in maintaining cell identity and restraining the progression of this lethal disease.
细胞可塑性是癌症的一个标志，使肿瘤细胞能够获得多种导致肿瘤进展、转移和治疗抵抗的表型。在本期《临床研究杂志》中，河合及其同事利用胰腺导管腺癌（PDAC）的基因工程小鼠模型（GEMM）证明，SWI/SNF复合物成员Pbrm1的缺失会驱动去分化和侵袭性肿瘤特征。Pbrm1的缺失激活了上皮-间质转化（EMT）程序，并导致出现低分化组织学特征，这些特征通常与高复发率和不良预后相关。这些发现揭示了SWI/SNF复合物在PDAC演变过程中在维持细胞特性和抑制这种致命疾病进展方面的作用。
