Intracellular trafficking and degradation of unassociated pro$alpha;2 chains of collagen type I

GOTKIN, M

doi:10.1016/s0014-4827(04)00065-5

Cited by 1 publication

(3 citation statements)

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“…However, it is also possible that intracellular lysosomal cathepsins can generate cryptic fragments of collagen inside the cell (Ishida & Nagata, 2009;Wagenaar-Miller et al, 2007). Interestingly, using novel zebrafish models and electron microscopy ima- isms, which collectively contribute to degrading and eliminating misfolded molecules (Gotkin, Ripley, Lamande, Bateman, & Bienkowski, 2004;Ishida & Nagata, 2009;Lee & Ye, 2018;Ponpuak et al, 2015).…”

Section: F I G U R Ementioning

confidence: 99%

“…Interestingly, studies have shown that newly synthesized collagen that is either mutated or misfolded can lead to rapid accumulation of abnormal aggregates that result in ER stress, which subsequently facilitate either autophagy-lysosomal mediated degradation or ERAD (Anelli & Sitia, 2008;Gotkin et al, 2004;Ishida & Nagata, 2009;Lee & Ye, 2018;Ponpuak et al, 2015). Recent studies have shown that local micro-unfolding of the collagen molecule due to mechanical tension may occur (Glentis et al, 2017;Spaderna et al, 2006).…”

Section: F I G U R Ementioning

confidence: 99%

“…A second mannose receptor family member uPARAP/ Endo-180 has also been shown to specifically internalize collagen for further cathepsin-mediated proteolytic degradation in lysosomes of stromal cells such as fibroblasts (Melander et al, 2015). The molecular mechanisms associated with collagen degradation as well as both conventional and unconventional protein secretion are becoming more well-defined within the endo-lysosomal compartments following ER stress, and include the unfolded protein response, ER-associated degradation (ERAD) and autophagic/lysosomal associated mechanisms, which collectively contribute to degrading and eliminating misfolded molecules (Gotkin, Ripley, Lamande, Bateman, & Bienkowski, 2004;Ishida & Nagata, 2009;Lee & Ye, 2018;Ponpuak et al, 2015).…”

Section: The Generation Of Cryptic Collagen Elementsmentioning

confidence: 99%

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Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis

Han

Caron

Brooks

2020

Journal Cellular Physiology

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Structural remodeling of the extracellular matrix is a well‐established process associated with tumor growth and metastasis. Tumor and stromal cells that compose the tumor mass function cooperatively to promote the malignant phenotype in part by physically interacting with intact and structurally altered matrix proteins. To this end, collagen represents the most abundant component of the extracellular matrix and is known to control the behavior of histologically distinct tumor types as well as a diversity of stromal cells. Although a significant molecular understanding has been established concerning how cellular interactions with intact collagen govern signaling pathways that control tumor progression, considerably less is known concerning how interactions with cryptic or hidden regions within remodeled collagen may selectively alter signaling cascades, or whether inhibition of these cryptic signaling pathways may represent clinically effective therapeutic strategies. Here, we review the emerging evidence concerning the possible mechanisms for the selective generation of cryptic or hidden elements within collagen and their potential cell surface receptors that may facilitate signal transduction. We discuss the concept that cellular communication links between cell surface receptors and these cryptic collagen elements may serve as functional signaling hubs that coordinate multiple signaling pathways operating within both tumor and stromal cells. Finally, we provide examples to help illustrate the possibility that direct targeting of these unique cryptic signaling hubs may lead to the development of more effective therapeutic strategies to control tumor growth and metastasis.

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