Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth

Iida, Joji; Dorchak, Jesse; Clancy, R. L.; Slavik, Juliana; Ellsworth, Rachel E.; Katagiri, Yasuhiro; Pugacheva, Elena N.; Kuppevelt, Toin H. Van; Mural, Richard J.; Cutler, Mary Lou; Shriver, Craig D.

doi:10.1016/j.yexcr.2014.11.002

Cited by 57 publications

(40 citation statements)

References 67 publications

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“…In this context, chondroitin sulfate has been implicated in tumor progression and metastasis via regulation of tumor cell adhesion, migration, and invasion [11,31,34]. In breast cancer, the role of CHST11 on tumor progression and metastasis has been previously described [4,10]. Here, CHST11-mediated regulation of CSPG4, which serves as P-selectin ligand through its CS chain, was observed.…”

Section: Discussionmentioning

confidence: 75%

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

et al. 2015

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Ovarian cancer (OvCa) accounts for the highest tumor-related mortality among gynecological malignancies, but the underlying mechanisms are poorly understood. Glycosaminoglycans are abundantly present in ovarian tumors, and there is rising evidence that chondroitin sulfate (CS) as well as diverse carbohydrate sulfotransferases (CHSTs), the enzymes involved in the sulfation process of these structures, plays an important role in metastatic spread of tumor cells. mRNA expression levels of CHST3/7/11/12/13/15 were compared between malignant (86 OvCas) and non-malignant tumors (6 borderline tumors and 3 cystadenomas). CHST11 and CHST15 were further chosen for Western blot analysis in a cohort of 216 OvCas. Protein expression levels were correlated with clinicopathologic prognostic parameters and survival data. A significantly higher mRNA expression of CHST11, CHST12, and CHST15 was measured in ovarian cancer samples in comparison to non-malignant ones, and the same trend was observed for CHST13. For CHST3 and CHST7, no significant differences were found between the two groups. At protein level, high CHST11 expression was independently associated with unfavorable progression-free survival (PFS; p = 0.027). A similar trend was observed for CHST15, showing a nearly significant correlation between high expression levels and shorter recurrence-free survival in patients without macroscopic residual tumor after surgery (p = 0.053). We conclude that CHSTs involved in the synthesis of CS-A and CS-E might influence ovarian cancer progression, and we suggest CHST11 as independent unfavorable prognostic factor in this entity.

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Section: Discussionmentioning

confidence: 75%

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

et al. 2015

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“…NEDD9 is abundantly expressed in many breast cancer cell lines [32]. Overexpression of NEDD9 promotes migration and invasion of breast tumor cells [56, 59, 60] through mechanisms that include activating proteins of the focal adhesion complex (FAK and SRC) [56], mediating effects of TGFβ [61–63], increasing the expression and activity of matrix metalloproteases (MMPs) [59, 64], regulating trafficking and enzymatic recovery of MMPs and integrins [65, 66] increasing synthesis of tumor-associated glycocalyx [67], and down-regulating E-cadherin [60, 68] (Fig. 3).…”

Section: Altered Nedd9 Expression In Cancermentioning

confidence: 99%

“…However, because NEDD9 serves as a scaffolding molecule for other signaling proteins that play significant roles in cancer development, the effects of NEDD9 overexpression in supporting metastasis could in theory be mitigated by inhibition of its upstream regulators or downstream targets. Inhibition of FAK and SRC has been suggested [73], as well as targeting MMPs [64] or removing chondroitin sulfate E by chondroitinase ABC [67]. Conversely, NEDD9 expression levels could influence response to drugs targeting its partners.…”

Section: Nedd9 and Cancer Therapymentioning

confidence: 99%

Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases

Shagisultanova

Gaponova

Gabbasov

et al. 2015

Gene

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Cancer progression requires a significant reprogramming of cellular signaling to support the essential tumor-specific processes that include hyperproliferation, invasion (for solid tumors) and survival of metastatic colonies. NEDD9 (also known as CasL and HEF1) encodes a multi-domain scaffolding protein that assembles signaling complexes regulating multiple cellular processes relevant to cancer. These include responsiveness to signals emanating from the T and B cell receptors, integrins, chemokine receptors, and receptor tyrosine kinases, as well as cytoplasmic oncogenes such as BCR-ABL and FAK- and SRC-family kinases. Downstream, NEDD9 regulation of partners including CRKL, WAVE, PI3K/AKT, ERK, E-cadherin, Aurora-A (AURKA), HDAC6, and others allow NEDD9 to influence functions as pleiotropic as migration, invasion, survival, ciliary resorption, and mitosis. In this review, we summarize a growing body of preclinical and clinical data that indicate that while NEDD9 is itself non-oncogenic, changes in expression of NEDD9 (most commonly elevation of expression) are common features of tumors, and directly impact tumor aggressiveness, metastasis, and response to at least some targeted agents inhibiting NEDD9-interacting proteins. These data strongly support the relevance of further development of NEDD9 as a biomarker for therapeutic resistance. Finally, we briefly discuss emerging evidence supporting involvement of NEDD9 in additional pathological conditions, including stroke and polycystic kidney disease.

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“…The large CS proteoglycan Versican is linked to poor prognosis in many different cancer types (Ricciardelli et al 2009b). CSGALNACT1 is upregulated by NEDD9 in breast cancer cells (Iida et al 2015) CSGALNACT1 is androgen regulated and required for prostate cancer cell viability . Versican is androgen regulated (Read et al 2007) and is linked to disease progression in early stage prostate cancer (Ricciardelli et al 1998).…”

Section: :3mentioning

confidence: 99%

Glycosylation is a global target for androgen control in prostate cancer cells

Munkley¹

2017

Endocrine-Related Cancer

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Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer. We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly upregulated in prostate cancer tissue. These 8 enzymes are under direct control of the androgen receptor (AR) and are linked to the synthesis of important cancer-associated glycans such as sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulfate. Glycosylation has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism. Our results suggest that alterations in patterns of glycosylation via androgen control might modify some or all of these processes in prostate cancer. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Emerging data on these often overlooked glycan modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer.

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Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth

Cited by 57 publications

References 67 publications

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases

Glycosylation is a global target for androgen control in prostate cancer cells

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