Abstract
Carcinogenesis is a multifactorial process with the input and interactions of environmental, genetic, and metabolic factors. During cancer development, a significant remodeling of the extracellular matrix (ECM) is evident. Proteoglycans (PGs), such as lumican, are glycosylated proteins that participate in the formation of the ECM and are established biological mediators. Notably, lumican is involved in cellular processes associated with tumorigeneses, such as EMT (epithelial-to-mesenchymal transition), cellular proliferation, migration, invasion, and adhesion. Furthermore, lumican is expressed in various cancer tissues and is reported to have a positive or negative correlation with tumor progression. This review focuses on significant advances achieved regardingthe role of lumican in the tumor biology. Here, the effects of lumican on cancer cell growth, invasion, motility, and metastasis are discussed, as well as the repercussions on autophagy and apoptosis. Finally, in light of the available data, novel roles for lumican as a cancer prognosis marker, chemoresistance regulator, and cancer therapy target are proposed.
Highlights
extracellular matrix (ECM) cues coordinate the different effectors of the tumor microenvironment (TME) and modulate the plethora of signaling pathways involved in the propagation of the “hallmarks of cancer” [2,11]
(f) Lumican induces the dimerization of the EGFR receptors and their subsequent uptake and degradation, leading to attenuated pancreatic ductal adenocarcinoma (PDAC) cell growth. (g) Hypoxia significantly reduces lumican secretion from pancreatic stellate cells and results in attenuated PDAC cell growth. (h) Lumican affects the signaling of Snail, an EMT trigger molecule that facilitates cancer metastasis, attenuating melanoma metastasis to the lungs
These results suggest that FOXO3 is a lumican biological partner that is important to neuroblastoma development
Summary
PGs are glycosylated proteins that participate in the formation of the ECM. These hybrid molecules consist of a protein core into which one or more GAG chains are covalently bound. Lumican is expressed in various cancer tissues and is reported to have a positive or negative correlation with tumor progression [26]. Many studies have shown that lumican modulates tumor cells’ proliferation, invasion, and metastasis with different mechanisms, either enhancing or preventing cancer progression. In an immunocompetent model of melanoma, implanted in Lum−/− vs wild type syngeneic mice, concluded that endogenous lumican modulates the organization of the tumor matrix regarding the intratumoral distribution of matrix proteins, growth factors, and stromal cells in a manner correlated with disease progression [68]. A recent study in breast cancer in vitro showed that lumican treatment in combination with the knockdown of ERα and the suppression of ERβ can regulate these cells’ differentiation state, morphology, expression of matrix effectors, and cell behavior [75]. (f) Lumican induces the dimerization of the EGFR receptors and their subsequent uptake and degradation, leading to attenuated PDAC cell growth. (g) Hypoxia significantly reduces lumican secretion from pancreatic stellate cells and results in attenuated PDAC cell growth. (h) Lumican affects the signaling of Snail, an EMT trigger molecule that facilitates cancer metastasis, attenuating melanoma metastasis to the lungs
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