Posts tagged epithelial-to-mesenchymal transition (EMT)
E273 Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration Screen reader support enabled.
E273 Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration Screen reader support enabled.

Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in ~10%
of neuroblastoma (NB) tumors, the role of the wild-type (WT) receptor, which is aberrantly expressed in most
non-mutated cases, is unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage.
Here, we map the cleavage site to Asn654-Leu655 and demonstrate that cleavage inhibition of WT ALK significantly impedes NB cell migration with subsequent prolongation of survival in mouse models. Cleavage inhibition results in the downregulation of an epithelial-to-mesenchymal transition (EMT) gene signature, with decreased nuclear localization and occupancy of b-catenin at EMT gene promoters. We further show that
cleavage is mediated by matrix metalloproteinase 9, whose genetic and pharmacologic inactivation inhibits
cleavage and decreases NB cell migration. Together, our results indicate a pivotal role for WT ALK ECD cleavage in NB pathogenesis, which may be harnessed for therapeutic benefit. READ ARTICLE

Cell Reports DOI:10.1016/J.CELREP.2021.109363

Authors: Hao Huang, Alexander Gont, Lynn Kee, Ruben Dries, Kathrin Pfeifer, Bandana Sharma, David N. Debruyne, Matthew Harlow, Satyaki Sengupta, Jikui Guan, Caleb M. Yeung, Wenchao Wang, Bengt Hallberg, Ruth H. Palmer, Meredith S. Irwin, Rani E. George

Read More
Pre-Clinical, group4Kirk SmithALK, receptor tyrosine kinase (RTK), neuroblastoma, cleavage, MMP-9, migration, epithelial-to-mesenchymal transition (EMT), wild-type ALK, extracellular domain
High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients
High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients

(1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short. (2) Methods: We applied an inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs/CTC clusters from patients with metastatic non-small-cell lung cancer (NSCLC). (3) Results: Using Labyrinth, CTCs (PanCK+/DAPI+/CD45−) were isolated from patients (n = 25). Heterogeneous CTC populations, including CTCs expressing epithelial (EpCAM), mesenchymal (Vimentin) or both markers were detected. CTCs were isolated from 100% of patients (417 ± 1023 CTCs/mL). EpCAM− CTCs were significantly greater than EpCAM+ CTCs. Cell clusters of ≥2 CTCs were obs..... READ ARTICLE

Cancers DOI:10.3390/cancers12010127

Authors: Mina Zeinali, Maggie Lee, Arthi Nadhan, Anvya Mathur, Casey Hedman, Eric Lin, Ramdane Harouaka, Max S. Wicha, Lili Zhao, Nallasivam Palanisamy, Mathias Hafner, Rishindra Reddy, Gregory P. Kalemkerian, Bryan J. Schneider, Khaled A. Hassan, Nithya Ramnath, Sunitha Nagrath

Read More
Pre-ClinicalKirk SmithCirculating tumor cells (CTCs), CTC clusters, non-small-cell lung cancer (NSCLC), inertial microfluidics, epithelial-to-mesenchymal transition (EMT)