Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation

Wang, Chen; Okita, Yukari; Zheng, Ling; Shinkai, Yasuhiro; Manevich, Lev; Chin, Jas Min; Kimura, Tomokazu; Suzuki, Hiroyuki; Kumagai, Yoshito; Kato, Mitsuyasu

doi:10.1111/cas.15090

Cited by 8 publications

(7 citation statements)

References 43 publications

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“…51 We have also reported that serine phosphorylation in the intracellular domain of GPNMB might be mediated by RTK pathways upon EGF or FGF-2 stimulation and be important for EMT and stemness genes' induction. 52 As mentioned above, FGFR3 activation is frequently found in bladder cancers. Therefore, it would be interesting to investigate the contribution of serine phosphorylation of GPNMB in acquisition of cellular motility in bladder cancers as well as those of the RGD motif and KLD.…”

Section: Discussionmentioning

confidence: 90%

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Kimura,

Okita,

Nagumo

et al. 2024

Pathology International

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Bladder cancer is one of the most common cancers among men worldwide. Although multiple genomic mutations and epigenetic alterations have been identified, an efficacious molecularly targeted therapy has yet to be established. Therefore, a novel approach is anticipated. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that is highly expressed in various cancers. In this study, we evaluated bladder cancer patient samples and found that GPNMB protein abundance is associated with high‐grade tumors, and both univariate and multivariate analyses showed that GPNMB is a prognostic factor. Furthermore, the prognosis of patients with high GPNMB levels was significantly poorer in those with nonmuscle invasive bladder cancer (NMIBC) than in those with muscle invasive bladder cancer (MIBC). We then demonstrated that knockdown of GPNMB in MIBC cell lines with high GPNMB inhibits cellular migration and invasion, whereas overexpression of GPNMB further enhances cellular migration and invasion in MIBC cell lines with originally low GPNMB. Therefore, we propose that GPNMB is one of multiple driver molecules in the acquisition of cellular migratory and invasive potential in bladder cancers. Moreover, we revealed that the tyrosine residue in the hemi‐immunoreceptor tyrosine‐based activation motif (hemITAM) is required for GPNMB‐induced cellular motility.

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Section: Discussionmentioning

confidence: 90%

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Kimura,

Okita,

Nagumo

et al. 2024

Pathology International

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“…[5] GPNMB gene is located on chromosome 7q15 and is involved in cell proliferation, apoptosis and differentiation. [6,7] Studies have shown that GPNMB expression is up-regulated in head and neck squamous cell carcinoma, and its high expression is associated with poor prognosis. [8] Huang et al [9] found that GPNMB was an independent prognostic factor for triple negative breast cancer recurrence and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Construction of a prognostic model for radical esophagectomy based on immunohistochemical prognostic markers combined with clinicopathological factors

Wang

et al. 2023

Medicine

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Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and lacks effective biomarkers to evaluate prognosis and treatment. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a protein highly expressed in ESCC tissues screened by isobaric tags for relative and absolute quantitation proteomics, which has significant prognostic value in a variety of malignant tumors, but its relationship with ESCC remains unclear. By immunohistochemical staining of 266 ESCC samples, we analyzed the relationship between GPNMB and ESCC. To explore how to improve the ability of ESCC prognostic assessment, we established a prognostic model of GPNMB and clinicopathological features. The results suggest that GPNMB expression is generally positive in ESCC tissues and is significantly associated with poorer differentiation, more advanced American Joint Council on Cancer (AJCC) stage, and higher tumor aggressiveness (P < .05). Multivariate Cox analysis indicated that GPNMB expression was an independent risk factor for ESCC patients. A total of 188 (70%) patients were randomly selected from the training cohort and the four variables were automatically screened by stepwise regression based on the AIC principle: GPNMB expression, nation, AJCC stage and nerve invasion. Through the weighted term, we calculate the risk score of each patient, and by drawing the receiver operating characteristic curve, we show that the model has good prognostic evaluation performance. The stability of the model was verified by test cohort. Conclusion: GPNMB is a prognostic marker consistent with the characteristics of tumor therapeutic targets. For the first time, we constructed a prognostic model combining immunohistochemical prognostic markers and clinicopathological features in ESCC, which showed higher prognostic efficacy than AJCC staging system in predicting the prognosis of ESCC patients in this region.Abbreviations: AJCC = American Joint Council on Cancer, AUC = area under the curve, ESCC = esophageal squamous cell carcinoma, GPNMB = glycoprotein nonmetastatic melanoma protein B, IHC = immunohistochemical, ITRAQ = isobaric tags for relative and absolute quantitation, OS = overall survival, ROC curve = receiver operating characteristic curve.

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“… 23 , 24 , 25 , 26 We have previously demonstrated the importance of GPNMB in tumorigenic functions such as growth in vitro and in vivo, cellular migration and invasion, and induction of stem‐like properties in breast cancer cells. 27 , 28 , 29 , 30 Although the oncogenic role of this protein was reported in some cancer types, little is known about GPNMB involvement in progression of HNSCC, especially LSCC. Previously, it was reported that GPNMB promotes migration of oral SCC (OSCC) and invasion of HNSCC, 31 , 32 while the contributory effects on tumorigenic function in LSCC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Glycoprotein NMB (GPNMB), a type 1 transmembrane protein reported to be involved in malignant progression of various cancers, such as melanoma, glioma, and triple‐negative breast cancer, may be such a target, as its high expression is thought to be a poor prognostic factor in those cancers 23–26 . We have previously demonstrated the importance of GPNMB in tumorigenic functions such as growth in vitro and in vivo, cellular migration and invasion, and induction of stem‐like properties in breast cancer cells 27–30 . Although the oncogenic role of this protein was reported in some cancer types, little is known about GPNMB involvement in progression of HNSCC, especially LSCC.…”

Section: Introductionmentioning

confidence: 99%

Glycoprotein NMB promotes tumor formation and malignant progression of laryngeal squamous cell carcinoma

et al. 2022

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Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth‐arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki‐67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy.

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Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation

Abstract: The global incidence of breast cancer has been on the rise since the late 1970s. [1][2][3] Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein, is highly expressed in various cancers, including breast cancer. A high level of GPNMB expression is

Cited by 8 publications

References 43 publications

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Construction of a prognostic model for radical esophagectomy based on immunohistochemical prognostic markers combined with clinicopathological factors

Glycoprotein NMB promotes tumor formation and malignant progression of laryngeal squamous cell carcinoma

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