Clinical Significance of SH2B1 Adaptor Protein Expression in Non-small Cell Lung Cancer

Zhang, Hang; Duan, Chaojun; Chen, Wei; Wang, Shaoqiang; Zhang, Sheng-Kang; Dong, Shuang; Cheng, Yuanda; Zhang, Chunfang

doi:10.7314/apjcp.2012.13.5.2355

Cited by 13 publications

(13 citation statements)

References 41 publications

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“…It has been demonstrated that SH2B1 acts as an oncogene in lung cancer, esophageal cancer and neuroblastoma (9)(10)(11)(12). However, its functions in GC remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…All three members share a common domain structure that includes a dimerization domain, a pleckstrin homology domain, several proline-rich regions and a SH2 domain near the C-terminus (7). Previous studies have demonstrated that SH2B1 contributes to the malignant progression of tumors, including colon, ovary and non-small cell lung tumors (8)(9)(10)(11)(12). However, the effect of SH2B1 expression on GC has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

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Circulating SH2B1 is associated with an increased risk of gastric cancer

Lundbäck

Zhao

et al. 2018

Oncol Lett

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Abstract. Gastric cancer (GC) is one of the most common types of cancer in humans and the second leading cause of cancer-associated mortality worldwide. Identifying novel risk factors will facilitate the development of therapeutic strategies to prevent and treat GC. Increased expression of the Src homology 2 B adaptor protein 1 (SH2B1) may stimulate the malignant progression of lung cancer, esophageal cancer and neuroblastoma. However, its function in GC has not yet been investigated. To identify whether increased serum SH2B1 is a risk factor for GC, the present study performed a nested case-control study of patients within the Chinese cohort study. Levels of serum SH2B1 were measured in 563 patients diagnosed with GC during the follow-up period and in 1,126 matched healthy controls. The results demonstrated that high levels of serum SH2B1 were associated with an increased GC risk (odds ratio, 3.23; 95% confidence interval, 2.45-5.65). When analyses were stratified further by sex, age and smoking, an association between increased levels of SH2B1 and GC was identified in males but not in females. Furthermore, the association between SH2B1 levels and GC was more evident in younger than in older participants, and statistically significant in current smokers but not in nonsmokers. These results were not altered following the exclusion of outliers. Furthermore, it was demonstrated that overexpression of SH2B1 contributes to the malignant transformation of normal gastric epithelial cells. Thus, the present study demonstrated that elevated serum SH2B1 levels may increase the risk of GC.

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“…It has been demonstrated that SH2B1 acts as an oncogene in lung cancer, esophageal cancer and neuroblastoma (9)(10)(11)(12). However, its functions in GC remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating SH2B1 is associated with an increased risk of gastric cancer

Lundbäck

Zhao

et al. 2018

Oncol Lett

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“…Many studies have demonstrated that adaptor proteins are also involved in oncogenic signal transduction pathways. For example, the expression of adaptor protein, SH2B1, is elevated in non-small cell lung cancer (NSCLC) tissues [47]. SH2B1's overexpression is considered to be an independent prognostic factor for patients with NSCLC [47].…”

Section: Clinical Significance Of Xb130 In Cancermentioning

confidence: 99%

XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis

et al. 2014

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Several adaptor proteins have previously been shown to play an important role in the promotion of tumourigenesis. XB130 (AFAP1L2) is an adaptor protein involved in many cellular functions, such as cell survival, cell proliferation, migration, and gene and miRNA expression. XB130's functional domains and motifs enable its interaction with a multitude of proteins involved in several different signaling pathways. As a tyrosine kinase substrate, tyrosine phosphorylated XB130 associates with the p85α regulatory subunit of phosphoinositol-3-kinase (PI3K) and subsequently affects Akt activity and its downstream signalling. Tumourigenesis studies show that downregulation of XB130 expression by RNAi inhibits tumor growth in mouse xenograft models. Furthermore, XB130 affects tumor oncogenicity by regulating the expression of specific tumour suppressing miRNAs. The expression level and pattern of XB130 has been studied in various human tumors, such as thyroid, esophageal, and gastric cancers, as well as, soft tissue tumors. Studies show the significant effects of XB130 in tumourigenesis and suggest its potential as a diagnostic biomarker and therapeutic target for cancer treatments.

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“…SH2B1 increases the ability of RET to promote transformation of NIH 3T3 cells [64] . SH2B1 is abnormally expressed in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines [70] . SH2B1 overexpression is associated with increased tumor grade, tumor size, lymph node metastasis in NSCLC patients [70] .…”

Section: Sh2b1 Promotes Mitogenesis and Transformationmentioning

confidence: 99%

SH2B1 regulation of energy balance, body weight, and glucose metabolism

Rui

2014

WJD

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The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo-or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and IRS2. SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/ IRS1/2 signaling complex. SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins. Accordingly, genetic deletion of SH2B1 results in severe leptin resistance, insulin resistance, hyperphagia, obesity, and type 2 diabetes in mice. Neuronspecific overexpression of SH2B1β transgenes protects against diet-induced obesity and insulin resistance. SH2B1 in pancreatic β cells promotes β cell expansion and insulin secretion to counteract insulin resistance in obesity. Moreover, numerous SH2B1 mutations are genetically linked to leptin resistance, insulin resistance, obesity, and type 2 diabetes in humans. Unlike SH2B1, SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis. The metabolic function of the SH2B family is conserved from insects to humans. Key words: Obesity; Type 2 diabetes; Leptin resistance; Insulin resistance; Glucose intolerance; Hypothalamus; Energy balance; Food intake; Hyperphagia; Nonalcoholic fatty liver disease Core tip: The Src homology 2B (SH2B) family members mediate cell signaling in response to a variety of hormones, cytokines, and growth factors. In the brain, SH2B1 enhances leptin signaling and leptin's antiobesity action. In peripheral tissues, SH2B1 cell-autonomously enhances insulin signaling. In pancreatic islets, SH2B1 is required for compensatory β cell expansion in response to insulin resistance and β cell stress. SH2B1-deficiency results in severe leptin resistance, energy imbalance, obesity, and type 2 diabetes. SH2B1 mutations are linked to leptin resistance, insulin resistance, obesity, and type 2 diabetes in humans. Thus, SH2B1 is a critical metabolic regulator in mammals.Rui L. SH2B1 regulation of energy balance, body weight, and glucose metabolism. World J Diabetes 2014; 5(4): 511-526 Available from:

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Clinical Significance of SH2B1 Adaptor Protein Expression in Non-small Cell Lung Cancer

Cited by 13 publications

References 41 publications

Circulating SH2B1 is associated with an increased risk of gastric cancer

Circulating SH2B1 is associated with an increased risk of gastric cancer

XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis

SH2B1 regulation of energy balance, body weight, and glucose metabolism

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