Matrix crosslinking forces tumor progression by enhancing integrin signaling (Cell, 2009, 139:891-906)

報告日期: 2010/03/19
報告時間: 16:00/16:50
報告學生: 黃俊豪(英文報告)
講評老師: 湯銘哲

Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Cell 139, 891–906, November 25, 2009


Kandice R. Levental, Hongmei Yu, Laura Kass, Johnathon N. Lakins, Mikala Egeblad, Janine T. Erler, Sheri F.T. Fong, Katalin Csiszar, Amato Giaccia, Wolfgang Weninger, Mitsuo Yamauchi, David L. Gasser, and Valerie M. Weaver


Speaker: Chun-Hau Huang

Commentator: Dr. Ming-Jer Tang

Date : 2010.3.19

Room : 602



Remodeling and stiffening of extracellular matrix (ECM) are associated with disease, including cancer. Collagen is the most abundant ECM in stroma and considered a barrier against tumor. However, increased expression of collagen is related to tumor malignancy. LOX mediated crosslinking increases tissue tensile strength and matrix stiffness. In results, the authors used MMTV-neu rat model to assess LOX-mediated collagen crosslinking was association with fibrosis, ECM stiffness, focal adhesion and tumor progression. In vitro, they used MCF10A cell line and added ribose to induce ECM stiffness and activated oncoprotein ErbB2 in 3D collagen I/ reconstituted basement membrane gel, the results showed that collagen crosslinking and ECM stiffening needed to cooperate with oncogene ErbB2 to promote breast tumor invasion and integrin signaling in force-dependent tumor progression. Further, they found that PI3K-Akt signaling increased in premalignant and malignant tissue and in ribose-stiffened collagen gels. This paper showed that ECM stiffness induced by raised collagen crosslinking and stiffness could promote breast malignancy by enhancing integrins and growth factor receptors crosstalk.


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