Mammalian Plakins, Giant Cytolinkers: Versatile Biological Functions and Roles in Cancer

Abstract

Cancer is a highly lethal disease that is characterized by aberrant cell proliferation, migration, and adhesion, which are closely related to the dynamic changes of cytoskeletons and cytoskeletal-adhesion. These will further result in cell invasion and metastasis. Plakins are a family of giant cytolinkers that connect cytoskeletal elements with each other and to junctional complexes. With various isoforms composed of different domain structures, mammalian plakins are broadly expressed in numerous tissues. They play critical roles in many cellular processes, including cell proliferation, migration, adhesion, and signaling transduction. As these cellular processes are key steps in cancer development, mammalian plakins have in recent years attracted more and more attention for their potential roles in cancer. Current evidence shows the importance of mammalian plakins in various human cancers and demonstrates mammalian plakins as potential biomarkers for cancer. Here, we introduce the basic characteristics of mammalian plakins, review the recent advances in understanding their biological functions, and highlight their roles in human cancers, based on studies performed by us and others. This will provide researchers with a comprehensive understanding of mammalian plakins, new insights into the development of cancer, and novel targets for cancer diagnosis and therapy.

The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden

“…The top ranked differentially methylated probe was cg04146982, BF 34.5, adjusted p value 5.67 × 10 –16 (chr8:144,943,810–144,943,810, hg19 coordinates), which tags a CpG dinucleotide 3651 bp upstream of the transcription start site of gene Epiplakin 1, (EPPK1) 60 . EPPK1 is part of the Plakin family an important component of the cell cytoskeleton 61 . The other DMP was cg12209861, BF 7.1, adjusted p value 0.059 (chr4:37,459,078–37,459,078, hg19 coordinates), 3526 bp upstream of the transcription start site of gene Chromosome 4 Open Reading Frame 19, ( C4orf19 ).…”

In-depth proteome analysis of more than 12,500 proteins in buffalo mammary epithelial cell line identifies protein signatures for active proliferation and lactation

“…In the brain, it acts through sonic hedgehog (SHH) signalling pathway and regulates the levels of effector molecules, including transcription activators-Gli1 and Gli2 83,84 . MACF1 is an actin-binding protein 85 , which is reported to play an essential role in the proliferation of neuronal progenitors through WNT/β-catenin and GSK-3 signalling pathways, during development of the nervous system 86 .…”

Biomedical potential of mammalian spectraplakin proteins: Progress and prospect

“…22 Beyond this, conditional KOs of MACF1 in the nervous system leads to neuronal migration and organization defects, 23 and when KOs of MACF1 in skin they lead to blistering or delayed recovery. 11,23 The implicated roles of the mammalian spectraplakins have led to the discovery that MACF1 produces at least six protein isoforms, 14,23 while BPAG1 produces seven, each with a presence in a large number of tissues. 14 As is the case with each of the other observed categories of spectraplakin isoforms, mammalian spectraplakins isoforms are some combination of the multiple domains coded within the gene 14 as outlined in Figure 1.…”

“…11,23 The implicated roles of the mammalian spectraplakins have led to the discovery that MACF1 produces at least six protein isoforms, 14,23 while BPAG1 produces seven, each with a presence in a large number of tissues. 14 As is the case with each of the other observed categories of spectraplakin isoforms, mammalian spectraplakins isoforms are some combination of the multiple domains coded within the gene 14 as outlined in Figure 1. Though the tissue distribution of each of these isoforms is known, some attributes such as the exact intracellular localization remain uncharacterized.…”

“…Though the tissue distribution of each of these isoforms is known, some attributes such as the exact intracellular localization remain uncharacterized. 14,24 The existence of spectraplakin genes throughout the metazoan clade and ultimately MACF1 and BPAG1 in mammals has been attributed to evolutionary conservation rather than independent development due to a large amount of apparent sequence homology. 16,25,26 Both the functions of spectraplakin isoforms and spectraplakin genes themselves in humans have been assayed to decipher their roles in the pathogenesis of certain diseases.…”