RHAMM/hyaluronan inhibit β-catenin degradation, enhance downstream signaling, and facilitate fibrosarcoma cell growth

Berdiaki, Aikaterini; Thrapsanioti, Lydia-Nefeli; Giatagana, Eirini-Maria; K. Karamanos, Nikos.; C. Savani, Rashmin; N. Tzanakakis, George; Nikitovic, Dragana

doi:10.1007/s11033-023-08763-0

Cited by 3 publications

(3 citation statements)

References 59 publications

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“…This interaction also affects the cytoskeletal organization by triggering the RHO‐ROCK pathway, which regulates the polymerization of actin and promotes cell unidirectional movement [158]. In this model, RHAMM is suggested to act as a scaffold protein binding β‐catenin and Axin‐2 at different cellular compartments to enhance β‐catenin transcriptional activity [159].…”

Section: Gags and Their Protein Moieties In Diseasementioning

confidence: 99%

A biological guide to glycosaminoglycans: current perspectives and pending questions

Ricard‐Blum,

Vivès,

Schaefer

et al. 2024

The FEBS Journal

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Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan sulfate (KS), and heparan sulfate (HS). It focuses on the major processes that remain to be deciphered to get a comprehensive view of the mechanisms mediating GAG biological functions. They include the regulation of GAG biosynthesis and postsynthetic modifications in heparin (HP) and HS, the composition, heterogeneity, and function of the tetrasaccharide linkage region and its role in disease, the functional characterization of the new PGs recently identified by glycoproteomics, the selectivity of interactions mediated by GAG chains, the display of GAG chains and PGs at the cell surface and their impact on the availability and activity of soluble ligands, and on their move through the glycocalyx layer to reach their receptors, the human GAG profile in health and disease, the roles of GAGs and particular PGs (syndecans, decorin, and biglycan) involved in cancer, inflammation, and fibrosis, the possible use of GAGs and PGs as disease biomarkers, and the design of inhibitors targeting GAG biosynthetic enzymes and GAG–protein interactions to develop novel therapeutic approaches.

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Section: Gags and Their Protein Moieties In Diseasementioning

confidence: 99%

A biological guide to glycosaminoglycans: current perspectives and pending questions

Ricard‐Blum,

Vivès,

Schaefer

et al. 2024

The FEBS Journal

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“…[16,36,[70][71][72] with complex signaling functions. RHAMM is well-documented to bind to HA fragments, [16,73] and as a peripheral exracellular protein, its ability to activate signaling pathways regulated by HA fragments results from an interaction with integral receptors. Reported interactions include growth factor, toll-like receptors, [74] and CD44.…”

Section: Rhamm/hmmrmentioning

confidence: 99%

“…[32,36] The co-association of RHAMM with CD44, which is perhaps the most documented extracellular interaction relevant to metastasis, has been verified by co-immunofluorescence, FRET, and co-immunoprecipitation. [45,75,76] Co-association depends upon the molecular weight and presentation (e.g., organization) of HA, [75] regulates signaling pathways (e.g., MEK1,2/ERK1,2, and CTNNB1) [16,73,77,78] and tunes responses of CD44 to HA, [76] which impact tumor cell functions contributing to metastasis including proliferation, survival, motility, and invasion. One mechanistic explanation for how this protein: protein interaction activates signaling pathways can be related to the binding preference of RHAMM for HA fragments.…”

Section: Rhamm/hmmrmentioning

confidence: 99%

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Tolg,

Hill,

Turley

2024

Advanced Biology

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The progression of primary tumors to metastases remains a significant roadblock to the treatment of most cancers. Emerging evidence has identified genes that specifically affect metastasis and are potential therapeutic targets for managing tumor progression. However, these genes can have dual tumor promoter and suppressor functions that are contextual in manifestation, and that complicate their development as targeted therapies. CD44 and RHAMM/HMMR are examples of multifunctional proteins that can either promote or suppress metastases, as demonstrated in experimental models. These two proteins can be viewed as microenvironmental sensors and this minireview addresses the known mechanistic underpinnings that may determine their metastasis suppressor versus promoter functions. Leveraging this mechanistic knowledge for CD44, RHAMM, and other multifunctional proteins is predicted to improve the precision of therapeutic targeting to achieve more effective management of metastasis.

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Hyaluronan Receptors: Role in Aging and Age-Associated Processes

Хабаров,

Дробинцева,

Кветная

et al. 2024

Успехи Геронтологии

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В обзоре описано участие разнообразных рецепторов гиалуроновой кислоты, включая CD44, RHAMM, HARE, TLR, LYVE-1, в поддержании гомеостаза в норме и при старении, а также в развитии возраст-ассоциированных воспалительных процессов (инфламэйджинга) и злокачественных опухолей. Показана связь активации рецепторов CD44 c иммунными клетками и развитием ИБС. Кроме того, показана связь рецептора CD44 и остеоартрита через TLR2 и TLR4. Описан онкогенный потенциал RHAMM в отношении рака молочной железы, предстательной железы, лейкемии, поджелудочной железы, легких и глиобластомы, причем наиболее сильную экспрессию наблюдают в метастатических опухолях. В экспериментах in vivo и in vitro установлено, что фрагменты гиалуроновой кислоты длиной 4–25 дисахаридов могут способствовать пролиферации лимфатических эндотелиальных клеток и лимфангиогенезу. Таким образом, рецепторы гиалуронанов играют важную роль в процессах старения через регуляцию инфламэйджинга и в развитии злокачественных новообразований. The review describes the involvement of various hyaluronic acid receptors, including CD44, RHAMM, HARE, TLR, LYVE-1, in maintaining normal homeostasis and aging, as well as in the development of age-associated inflammatory processes (inflamaging) and malignant tumors. The association of CD44 receptor activation with immune cells and the development of coronary heart disease has been shown. In addition, a link between the CD44 receptor and osteoarthritis has been shown, via TLR2 and TLR4. The oncogenic potential of RHAMM in relation to breast, prostate, leukemia, pancreas, lung and glioblastoma cancers has been described, with the strongest expression observed in metastatic tumors. In vivo and in vitro experiments, it was found that fragments of hyaluronic acid with a length of 4 to 25 disaccharides can contribute to the proliferation of lymphatic endothelial cells and lymphangiogenesis. Thus, hyaluronic acid receptors play an important role in the aging process through the regulation of inflamaging and in the development of malignant neoplasms.

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RHAMM/hyaluronan inhibit β-catenin degradation, enhance downstream signaling, and facilitate fibrosarcoma cell growth

Cited by 3 publications

References 59 publications

A biological guide to glycosaminoglycans: current perspectives and pending questions

A biological guide to glycosaminoglycans: current perspectives and pending questions

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Hyaluronan Receptors: Role in Aging and Age-Associated Processes

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