Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors

Vasconcelos, Artur Cunha; Wagner, Vivian Petersen; Meurer, Luíse; Vargas, Pablo Agustı́n; Souza, Lélia Batista de; Fonseca, Felipe Paiva; Squarize, Cristiane H.; Castilho, Rogerio M.

doi:10.1016/j.oooo.2015.04.003

Cited by 4 publications

(5 citation statements)

References 56 publications

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“…The activated Akt stimulates the phosphorylation of downstream target proteins, suppresses autophagy and increases the resistance to apoptosis. These events promote gastric tumor cell proliferation and invasion ( 19 – 22 , 29 ). The results of the present study demonstrated that the expression of PI3K was higher in GC tissues than in normal gastric mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…Akt-mediated regulation of autophagy and tumorigenesis is achieved through Beclin-1 phosphorylation ( 18 ). Previous studies have suggested that the c-Met/PI3K signaling pathway is particularly active in tumors of the salivary glands, osteosarcoma, ovarian cancer and cervical cancer ( 19 – 22 ). Whether the c-Met/PI3K signaling pathway and the associated suppression of autophagy are involved in CagA-positive H. pylori infection-associated GC has yet to be established.…”

Section: Introductionmentioning

confidence: 99%

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Clinical value of CagA, c‑Met, PI3K and Beclin‑1 expressed in gastric cancer and their association with prognosis

et al. 2017

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Gastric cancer (GC) is the fourth most common type of malignant tumor worldwide, and causes the second highest number of cancer-associated mortalities in 2012. Gastric tumorigenesis is a multistep and multifactorial process. In the present study, tissue microarray and immunohistochemistry analysis were used to detect cytotoxin-associated gene A (CagA), c-Met, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and Beclin-1 expression in 121 GC tumors and 120 normal gastric tissues. The clinical relevance and prognostic implications of CagA, c-Met, PI3K and Beclin-1 expression in GC patients were analyzed. Furthermore, the Cox proportional hazards model was performed to indicate the independent prognostic factors for GC patients, including various clinicopathological parameters and CagA, c-Met, PI3K and Beclin-1 expression. The results indicated that CagA-positive H. pylori infection, c-Met, PI3K and Beclin-1 may have major roles in the oncogenesis, invasion and lymph node metastasis of GC. The disease-free survival rate was negatively associated with the expression of c-Met and CagA in tissues, and was positively associated with Beclin-1 expression. Overall survival was also negatively associated with the expression of c-Met and PI3K, and was positively associated with Beclin-1 expression. This indicated that c-Met and Beclin-1 may be independent and efficient biomarkers for predicting the DFS of patients with GC. Furthermore, in CagA-positive H. pylori infection-associated GC, c-Met expression was significantly upregulated and Beclin-1 expression was significantly downregulated. CagA-positive H. pylori infection therefore associated with the c-Met signaling pathway and the suppression of autophagy in the neoplasia, invasion and metastasis of GC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical value of CagA, c‑Met, PI3K and Beclin‑1 expressed in gastric cancer and their association with prognosis

et al. 2017

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“…In both cases, the combination of Met and PI3K or mTOR inhibitors reduced tumor growth in vivo better than with a single agent. The level of Met expression and Akt phosphorylation were investigated in human salivary gland tumors and were found to correlate (Vasconcelos et al, 2015 ).…”

Section: Targeting Met and Pi3k/akt/mtor Pathway In Cancermentioning

confidence: 99%

The Role of PI3K in Met Driven Cancer: A Recap

Hervieu

Kermorgant

2018

Front. Mol. Biosci.

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The Receptor Tyrosine Kinase (RTK) Met, overexpressed or mutated in cancer, plays a major role in cancer progression and represents an attractive target for cancer therapy. However RTK inhibitors can lead to drug resistance, explaining the necessity to develop therapies that target downstream signaling. Phosphatidylinositide 3-kinase (PI3K) is one of the most deregulated pathways in cancer and implicated in various types of cancer. PI3K signaling is also a major signaling pathway downstream of RTK, including Met. PI3K major effectors include Akt and “mechanistic Target of Rapamycin” (mTOR), which each play key roles in numerous and various cell functions. Advancements made due to the development of molecular and pharmaceutical tools now allow us to delve into the roles of each independently. In this review, we summarize the current understanding we possess of the activation and role of PI3K/Akt/mTOR, downstream of Met, in cancer.

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“…The canonical signalling pathway of AR is composed of different phases: binding of androgens to AR, dissociating from heat‐shock proteins, translocating to the nucleus with formation of AR homodimers, binding to androgen response elements (AREs) within the promoter region of AR target genes, recruitment of coactivators and transcription of target genes . This pathway can interact with other oncogenic signalling pathways such as AKT/mTOR/PI3K, EGFR, HER2/Neu, Wnt which are involved in promoting growth and resistance in different malignancies, including salivary gland carcinomas . Targeting AR‐signalling pathway, due to its multitude of effects, might have beneficial effects in target therapy of SGCs.…”

Section: Biology Of Androgen Receptormentioning

confidence: 99%

“…14 This pathway can interact with other oncogenic signalling pathways such as AKT/mTOR/PI3K, EGFR, HER2/Neu, Wnt [15][16][17][18][19][20][21] which are involved in promoting growth and resistance in different malignancies, including salivary gland carcinomas. 22 Targeting AR-signalling pathway, due to its multitude of effects, might have beneficial effects in target therapy of SGCs.…”

Section: Biology Of and Rogen Receptormentioning

confidence: 99%

Androgen receptor in salivary gland carcinoma: A review of an old marker as a possible new target

Yeoh

Dabab

Rigby

et al. 2018

J Oral Pathology Medicine

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The role of the androgen receptor (AR) as an immunomarker for diagnosis of salivary gland duct carcinoma (SDC) is well known. Other non-squamous cell head and neck cancers (NSCC-HN), including a small subset of salivary gland cancers (SGCs), can also express AR. With the increase in effective and powerful new generation of anti-androgen agents and drugs administered orally, more targetable AR-driven NSCC-HN, such as subsets of SGCs, should be investigated for possible expression of AR. In this review, we focus on SGC subtypes, which could express AR and describe the main androgen deprivation therapy (ADT) strategies.

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Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors

Cited by 4 publications

References 56 publications

Clinical value of CagA, c‑Met, PI3K and Beclin‑1 expressed in gastric cancer and their association with prognosis

Clinical value of CagA, c‑Met, PI3K and Beclin‑1 expressed in gastric cancer and their association with prognosis

The Role of PI3K in Met Driven Cancer: A Recap

Androgen receptor in salivary gland carcinoma: A review of an old marker as a possible new target

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