Stromal rigidity stress accelerates pancreatic intraepithelial neoplasia progression and chromosomal instability via nuclear PTK2 localization
Since the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single -cell datasets revealed that the ECM shapes an alternate route of acinar-ductal transdifferentiation of acinar cells into a central hub of elegantly restrained TOP2A-overexpressing cancer cells that spread out as unique cancer clusters with copy number amplifications in MYC-PTK2 locus and PIK3CA.
Source: American Journal of Pathology - Category: Pathology Authors: Li-Yun Ding, Chia-Jung Chang, Szu-Ying Chen, Kuan-Lin Chen, Yueh-Shan Li, Yun-Chieh Wu, Ting-Yi Hsu, Hsin-Yu Ying, Hsin-Yi Wu, Michael, W. Hughes, Chia-Yih Wang, Chih-Han Chang, Ming-Jer Tang, Woei-Jer Chuang, Yan-Shen Shan, Chia-Jung Chang, Po-Hsien Huan Tags: Regular Article Source Type: research
More News: Cancer | Cancer & Oncology | Chia | Gastroschisis Repair | Pancreas | Pancreatic Cancer | Pathology