Abstract
Intermediate filament (IF) proteins make up the largest family of cytoskeletal proteins in metazoans, and are traditionally known for their roles in fostering structural integrity in cells and tissues. Remarkably, individual IF genes are tightly regulated in a fashion that reflects the type of tissue, its developmental and differentiation stages, and biological context. In cancer, IF proteins serve as diagnostic markers, as tumor cells partially retain their original signature expression of IF proteins. However, there are also characteristic alterations in IF gene expression and protein regulation. The use of high throughput analytics suggests that tumor-associated alterations in IF gene expression have prognostic value. Parallel research is also showing that IF proteins directly and significantly impact several key cellular properties, including proliferation, death, migration, and invasiveness, with a demonstrated impact on the development, progression, and characteristics of various tumors. In this review, we draw from recent studies focused on three IF proteins most associated with cancer (keratins, vimentin, and nestin) to highlight how several “hallmarks of cancer” described by Hanahan and Weinberg are impacted by IF proteins. The evidence already in hand establishes that IF proteins function beyond their classical roles as markers and serve as effectors of tumorigenesis.
Highlights
For example, nestin expression in tumors of human patients was shown to be significantly associated with aggressive cancer type with stem-like features [99]
intermediate filament (IF) protein expression often becomes altered under inflamed tissue settings relative to homeostatic controls; such is the case for keratins in tumor-derived epithelia, as well as for vimentin and nestin in immune cell populations
IF proteins take on an active role in cancer development, progression, and metastasis
Summary
The intermediate filament (IF) family of proteins is composed of 73 genes, making it the most diverse family of cytoskeletal proteins, which includes microtubules and actin filaments [1]. IF proteins serve an important role in that they maintain critical structural integrity of cells and tissues This is illustrated by mutations in IF genes, which result in structural abnormal filament and directly cause a by wide range of rare diseases thatresult manifest integrity of cells and formation tissues. The 54 keratin genes with 28 type I and 26 type II sequences are regulated so that Type I and II keratins heterodimerize and undergo further polymerization to form filaments, leading to a requirement for pairwise regulation at the transcriptional and post-translational levels [5] As it is for the IF family as a whole, not all keratins are expressed in a given cell. Nestin has been found to be expressed in cancer stem-like cells and poorly differentiated cancer cells [19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
