AFDN

Last update 23 Jan 2025

Basic Info

Synonyms

AF-6, AF6, Afadin

+ [6]

Introduction

Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011).

100 Clinical Results associated with AFDN

100 Translational Medicine associated with AFDN

0 Patents (Medical) associated with AFDN

494

Literatures (Medical) associated with AFDN

01 Dec 2024·Journal of Cell Science

The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

Article

Author: McParland, Emily D. ; Butcher, T. Amber ; Slep, Kevin C. ; Johnson, Ruth I. ; Bhattarai, Abhi ; Jensen, Corbin C. ; Gurley, Noah J. ; Peifer, Mark ; Wolfsberg, Leah R.

ABSTRACTDuring development cells must change shape and move without disrupting dynamic tissue architecture. This requires robust linkage of cell–cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian afadin play key roles in the regulation of such linkages. One central task for the field is defining mechanisms by which upstream inputs from Ras-family GTPases regulate Canoe and afadin. These proteins are unusual in sharing two tandem Ras-association (RA) domains – RA1 and RA2 – which when deleted virtually eliminate Canoe function. Work in vitro has suggested that RA1 and RA2 differ in GTPase affinity, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and that their conserved N-terminal extensions enhance binding. We created Drosophila canoe mutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function, whereas mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of the regulation of adherens junction–cytoskeletal linkages.

01 Nov 2024·Histology and histopathology

Establishment of human acute monocytic leukemia model with systemic infiltration in NPG mice.

Article

Author: Wu, Qiong ; Rao, Yanfei ; Tang, Aiping ; Sun, Wanlei ; Li, Zhenjiang ; Zheng, Jifu ; Xu, Jing ; Wang, Qingming ; He, Wenfeng

A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×10⁷ cells (group A) or 5×10⁷ cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry. The median survival of mice in groups A and B were 33.0 and 30.0 days, respectively. Blast cells in peripheral blood appeared on day 14 in group B, and on day 21 in group A. In addition, SHI-1 cell specific MLL-AF6 mRNA was detected in both spleen and bone marrow on day 14 post-inoculation. 21 days after inoculation, we observed human CD45⁺CD33⁺ cells with an SH-1-immunophenotype in the peripheral blood, spleen, and bone marrow, as well as solid neoplasms in multiple organs. Moreover, the histologically infiltrated leukemic cells expressed CD45. In conclusion, the current study demonstrated the normal growth of SHI-1 cells in the NPG mice without immunosuppression, which caused systemic leukemia similar to that observed in acute leukemia patients. We developed an efficient and reproducible model to study leukemia pathogenesis and progression.

01 Oct 2024·Cancer Research

AFDN Deficiency Promotes Liver Tropism of Metastatic Colorectal Cancer

Article

Author: Zhang, Honghe ; Tang, Zhe ; Liao, Shaoxia ; Han, Fengyan ; Deng, Mengli ; Chen, Chaoyi ; Pan, Lvyuan ; Ye, Kehong ; Lai, Maode ; Deng, Jingwen ; Wu, Chenxia

AbstractLiver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-wide CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell–cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer.Significance: A CRISPR screen reveals AFDN loss as a mediator of liver tropism in colorectal cancer metastasis by decreasing tight junctions in the primary tumor and increasing interactions between cancer cells and hepatocytes.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

AFDN

Basic Info

Related

Analysis