Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma

Yy, Jiang; Li, Shang; Zz, Shi; Tt, Zhang; Ma, Shaohua; Chen, Lu; Zhang, Y; Jj, Hao; Shi, Changhong; F, Shi; Xu, Xiaopeng; Cai, Yuchen; Xm, Jia; Zhan, Qimin; Wang, Ming Rong

doi:10.1038/onc.2016.17

Cited by 39 publications

(43 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, in the present study, low MAP4 expression was significantly associated with lower grade ( χ 2 = 22.933, df = 2, P < 0.001) which has also been observed in bladder cancer ( n = 34) (Ou et al 2014). Although a higher level of MAP4 mRNA was found in non-small cell lung carcinomas when compared to normal lung tissues (Cucchiarelli et al 2008) and MAP4 expression was associated with shorter survival of the esophageal squamous cell carcinoma patients ( n = 364) (Jiang et al 2016), no significant association was detected in the present study between MAP4 expression and overall survival in either the whole cohort or any of the subgroups tested.…”

Section: Discussioncontrasting

confidence: 66%

Expression of Syk and MAP4 proteins in ovarian cancer

Zhang

Deen

Storr

et al. 2019

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

PurposeWe have previously reported on the prognostic importance of the calpain family of proteins in ovarian cancer, especially calpain-2. Spleen tyrosine kinase (Syk) phosphorylates a variety of cytoskeletal proteins with studies suggesting potential interactions between Syk and conventional calpains. Microtubule-associated protein 4 (MAP4) has been reported to be regulated by Syk.MethodsThe current study assessed Syk and MAP4 protein expression, by immunohistochemistry on a tissue microarray comprised of cores from primary ovarian carcinomas (n = 575), to evaluate associations with patient clinical outcomes and other clinicopathological factors and sought to determine whether there were any correlations between the expression of Syk, MAP4 and the calpain system.ResultsMAP4 expression was significantly associated with ovarian cancer histological subtype (P < 0.001), stage (P = 0.001), grade (P < 0.001) and residual tumour (P = 0.005). Despite this finding, we found no significant association existing between MAP4 expression and overall survival. Syk expression was also found significantly associated with histological subtype (P < 0.001). Syk seems to play a contradictory role with respect to tumour progression: low cytoplasmic Syk expression was significantly associated with low stage (P = 0.013), and low nuclear Syk expression with chemo-resistance in patients treated with taxane-containing therapy (P = 0.006). Interestingly, despite the lack of association in the whole cohort, high nuclear Syk expression was significantly associated with better overall survival in certain subgroups (P = 0.001).ConclusionsThe current study indicates a lack of correlation between calpain-2 expression and Syk and MAP4. Syk, MAP4 and calpain-1 appeared to significantly correlate with each other in the whole cohort, with calpain-1 being more highly associated with MAP4 and Syk in mucinous carcinomas. Overall, the current results suggest that Syk, MAP4, and calpain-1 expression are correlated with each other and these proteins may be involved in early stages of tumour spread.Electronic supplementary materialThe online version of this article (10.1007/s00432-019-02856-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussioncontrasting

confidence: 66%

Expression of Syk and MAP4 proteins in ovarian cancer

Zhang

Deen

Storr

et al. 2019

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Judah Folkman verificated that tumor growth is dependent on the angiogenesis.He found that the diffuse substances secreted by the tumor can stimulate the proliferation of endothelial cells， and then form new blood vessels, and the tumor must form new blood vessels to provide nutrients after growing for more than a few millimeters [18]. It has been commal accepted that VEGF-A is the earliest discovered and most important pro-angiogenic factor [ 19 ].It has been demonstrated that VEGF overexpression potentiates the migratory and invasive ability of ESCC cells [20]，which coincides with observations in other malignancies [21] and proliferation via activating cell signaling [23].Early studies have confirmed a positive correlation between IL-1β secretion in gastric cancer and NF-κB activation in tumors [24].Another study also reported that infection with H. pylori and IL-1β deficient mice does not activate gastric mucosal inflammation and NF-κB in epithelial cells [25].IL-1RA inhibits IL-1's tumor-promoting function by blocking IL-1 binding to its receptor [26].Our results show that overexpression of IL-1RA can reduce the phosphorylation level of PI3k in cells and further reduce the expression of NF-κB and it's phosphorylation, suggesting that IL-1RA may play a role through the PI3K/NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

IL-1RA controls the development of esophageal cancer by inhibition of VEGF via PI3K/NF-κB signaling pathway

Shen

et al. 2019

Preprint

View full text Add to dashboard Cite

1.Abstract has been reported to function as tumor suppressor in a variety of tumors,but its function and mechanism in esophageal cancer remains largely unknown.Our previous studies have shown that IL-1RA is downregulated in primary esophageal cancer(EC), and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. In this study, we observed that over-expression of IL-1RA inhibits proliferation, migration, and tumor growth in esophageal cancer cells(ESCC), inhibits the expression and secretion of VEGF, and inhibits tumor angiogenesis. Further studies have shown the overexpression of IL-1RA inhibits the transmission of PI3K/NF-kappaB. Taken together, this study shows that IL-1RA can regulating the development of esophageal cancer by inhibiting VEGF expression and secretion via inhibiting PI3K/NF-kappaB signaling, and it may serve as a potential prognostic marker and therapeutic target for EC.

show abstract

“…MAP4 (microtubule-associated protein 4), a major non-neuronal MAP, promotes microtubule assembly and counteracts destabilization of interphase microtubule catastrophe promotion. MAP4 interacts with cyclin B, which targets cell division cycle 2 (CDC2) kinase to microtubules [38,39]. [39].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis and comparison of two bone marrow stromal cell lines using the SILAC method

Wan

Zhang

et al. 2016

Experimental Hematology

View full text Add to dashboard Cite

Two human bone marrow stromal cell lines, HS5 and HS27a, co-cultured with myeloid cells, have frequently been used in studies of cross talk between cells in the bone marrow microenvironment and hematopoietic cells. Altered expression of proteins is typically associated with cell-cell signal transduction and regulation of cellular functions. Many studies have focused on key proteins that contribute to functional differences in cell co-culture models, but global quantitative proteome analysis of HS5 and HS27a has not been performed. We employed the stable isotope labeling by amino acids in cell culture (SILAC) method using two stable isotopes each of arginine and lysine to label proteins in the two cell lines. Labeled proteins were analyzed by 2-D ultrahigh-resolution liquid chromatography- LTQ/Orbitrap mass spectrometry. Among 4,213 unique identified and annotated proteins in the cell lines, 1,462 were detected in two independent experiments. Of these, 69 exhibited significant upregulation and 48 significant downregulation (>95% confidence) in HS27a relative to HS5 cells. Gene ontology term and pathway analysis indicated that the differentially regulated proteins were involved in cellular movement, cell-to-cell signaling and interaction, and hematologic system development and function. A total of 55 items were identified in both genomic and proteomic databases. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed on 7 proteins randomly selected from 28 differentially expressed proteins that were identified in both databases and were involved in the top networks/pathways. We observed a decrease in apoptosis in co-cultured KG1a cells when integrin αV was inhibited in HS27a cells, which suggested the functional role of integrin αV in the co-culture system. The integrated genomic/proteomic approach described here, and the identified proteins, will provide a useful basis for further elucidation of molecular mechanisms in the bone marrow microenvironment and for ongoing studies of cross talk among stromal cells and myeloma cells in co-culture systems.

show abstract

Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma

Cited by 39 publications

References 36 publications

Expression of Syk and MAP4 proteins in ovarian cancer

Expression of Syk and MAP4 proteins in ovarian cancer

IL-1RA controls the development of esophageal cancer by inhibition of VEGF via PI3K/NF-κB signaling pathway

Quantitative proteomic analysis and comparison of two bone marrow stromal cell lines using the SILAC method

Contact Info

Product

Resources

About