Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1

Chang, Yingwei; Li, Li; Zhang, Luping; Guo, Xijing; Feng, Zhuoying; Zhou, Junchen; Zhou, Shuai; Feng, Guoying; Han, Fengchan; Huang, Wenhua; Yang, Jun; Huang, Fei

doi:10.1007/s13277-016-4849-9

Cited by 9 publications

(15 citation statements)

References 29 publications

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“…In cooperation with bFGF/VEGF, αvβ3/αvβ5 also activate signalling pathways (FAK/ILK, PI3K/Akt and SDF1-CXCR4 [ 78 ]) that promote EC proliferation, survival and migration [ 30 ]. Regarding PI3K/Akt, a recent study associates this pathway with Plexin-B1/Rho/αvβ3 and Serine/arginine Protein Kinase-1 [ 79 ]. Moreover, migration can be improved by αvβ3 interaction with pleiotrophin (a secreted heparin-binding cytokine) on GB cells and EC [ 80 ] and with the cell adhesion molecule L1CAM on GIC [ 81 ].…”

Section: Roles Of Integrins In Glioblastomamentioning

confidence: 99%

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

et al. 2017

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Glioblastomas are malignant brain tumors with dismal prognosis despite standard treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a particular subpopulation of Glioblastoma-initiating cells, which recapitulate the heterogeneity of the original Glioblastoma. In order to classify these heterogeneous tumors, genomic profiling has also been undertaken to classify these heterogeneous tumors into several subtypes. Current research focuses on developing therapies, which could take into account this cellular and genomic heterogeneity. Among these targets, integrins are the subject of numerous studies since these extracellular matrix transmembrane receptors notably controls tumor invasion and progression. Moreover, some of these integrins are considered as membrane markers for the Glioblastoma-initiating cells subpopulation. We reviewed here integrin expression according to glioblastoma molecular subtypes and cell heterogeneity. We discussed their roles in glioblastoma invasion, angiogenesis, therapeutic resistance, stemness and microenvironment modulations, and provide an overview of clinical trials investigating integrins in glioblastomas. This review highlights that specific integrins could be identified as selective glioblastoma cells markers and that their targeting represents new diagnostic and/or therapeutic strategies.

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Section: Roles Of Integrins In Glioblastomamentioning

confidence: 99%

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

et al. 2017

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“…Besides ERK and AKT, SRPK1 can activate several other tumor-related proteins in distinct tumor types, such as JNK [ 27 ] and VEGFs [ 28 – 30 ]. Certain up-stream regulators for SRPK1 were also identified, including RhoA [ 31 ], Wnt [ 15 ], TGF-β [ 27 ], long non-coding RNAs [ 25 ] and human papillomavirus type 1 E1^E4 protein [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Serine-arginine protein kinase 1 (SRPK1) is elevated in gastric cancer and plays oncogenic functions

Wei

Wang

et al. 2017

Oncotarget

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Serine-arginine protein kinase 1 (SRPK1) phosphorylates proteins involved in the regulation of several mRNA processing pathways including alternative splicing. SRPK1 has been reported to be over-expressed in multiple cancers including prostate, breast, lung and glioma. Several studies further identified that inhibition of SRPK1 showed tumor-suppressive effects, thus raising SRPK1 as a novel candidate chemotherapy target. Interestingly, SRPK1 plays tumor suppressing role in mouse embryonic fibroblasts, on that SRPK1-silencing induces cell transformation. Therefore, the effect of SRPK1 seems heterogeneously in different cell types and tissues. The existence and role of SRPK1 in gastric cancer (GC) hasn’t been reported. Here we investigated the expression pattern of SRPK1 in GC by immunohistochemistry and found that it was up-regulated in tumor tissues, where its expression was correlated with tumor grade and prognosis. Further, we explored the signaling mechanism of SRPK1 in promoting GC progression, which revealed that both PP2A and DUSP6 phosphatases impaired the oncogenic effects of SRPK1. However, we didn’t find any direct interaction between SRPK1 with PP2A or DUSP6, indicating PP2A and DUSP6 function by regulating the downstream effectors of SRPK1. Our study not only revealed the clinical significance of SRPK1 in GC, but also provided new evidence for its signaling modulation which is invaluable for novel chemotherapy development.

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“…The plexin-B1/SRPK1 pathway regulates cell motility, apoptosis, and angiogenesis [69] ↑SRPK1 was found in glioma cell lines ↓SRPK1 suppressed cell viability and response to chemotherapy in vitro [52] ↑SRPK1 was found in glioma cell lines ↓SRPK1 suppressed apoptosis in vivo and in vitro, also migration and invasion in vivo SRPK1 interacts with the PI3K/Akt pathway and modulates the expression of MMP-2 and MMP-9 [70]…”

Section: ↓Srpk1 Suppressed Migration and Invasion In Vitromentioning

confidence: 99%

“…The most conflicting results from SRPK1 downregulation were derived from glioma studies. Although it suppressed proliferation, migration, invasion, angiogenesis, and cell cycle progression, SRPK1 downregulation also suppressed apoptosis and at the same time induced resistance to chemotherapy in preclinical glioma studies [51,52,69,70]. Therefore, SRPK1 inhibition would require more caution if applied in brain cancers, as it could result in both tumor-suppressive and -promotive effects.…”

Section: Srpk1-mediated Mechanism(s)/ Pathway(s) Involved Referencementioning

confidence: 99%

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Nikas

Themistocleous

Paschou

et al. 2019

Cells

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Cancer, a heterogeneous disease composed of tumor cells and microenvironment, is driven by deregulated processes such as increased proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis. Alternative splicing, a mechanism led by splicing factors, is implicated in carcinogenesis by affecting any of the processes above. Accumulating evidence suggests that serine-arginine protein kinase 1 (SRPK1), an enzyme that phosphorylates splicing factors rich in serine/arginine domains, has a prognostic and potential predictive role in various cancers. Its upregulation is correlated with higher tumor staging, grading, and shorter survival. SRPK1 is also highly expressed in the premalignant changes of some cancers, showing a potential role in the early steps of carcinogenesis. Of interest, its downregulation in preclinical models has mostly been tumor-suppressive and affected diverse processes heterogeneously, depending on the oncogenic context. In addition, targeting SRPK1 has enhanced sensitivity to platinum-based chemotherapy in some cancers. Lastly, its aberrant function has been noted not only in cancer cells but also in the endothelial cells of the microenvironment. Although the aforementioned evidence seems promising, more studies are needed to reinforce the use of SRPK1 inhibitors in clinical trials. major area of research in the field of intratumor heterogeneity, while their presence is associated with cancer recurrence, metastasis, and resistance to chemotherapy [7].Cancer prognosis depends on multiple factors that affect survival. Tumor staging, traditionally performed with the TNM system, is the most important prognostic factor. It refers to the size of the tumor (T), also the extent of its spread to the regional lymph nodes (N) or distant metastatic sites (M) [8,9]. Grading refers to the histologic picture of the tumor, more specifically, how closely it looks compared to the normal tissue it derives from (differentiation) [10,11]. Both the presence of distant metastases (e.g., in lungs, brain, liver, bones) and poor differentiation are associated with a dismal prognosis [9,11]. The molecular subtype of specific cancers is also critical for cancer survival. For instance, breast cancer has diverse intrinsic subtypes-luminal A and B, human epidermal growth factor receptor 2-enriched (HER2-enriched), and basal-like-that directly impact prognosis [12][13][14]. Luminal breast cancers are most commonly hormone-positive, overexpressing estrogen receptors (ER), and are associated with a better prognosis than HER2-enriched or basal-like breast cancers (BLBCs) [12][13][14][15]. BLBCs, which most commonly present with a triple-negative phenotype, have been linked with the worst prognosis and highest metastatic potential of all breast cancer molecular subtypes [13,16,17].Alternative splicing is the process that removes introns and adds exons in various combinations resulting in multiple mRNA products hence protein transcripts. As a result, it maintains the protein diversity and cellular homeostasis [18]. The...

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Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1

Cited by 9 publications

References 29 publications

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

Serine-arginine protein kinase 1 (SRPK1) is elevated in gastric cancer and plays oncogenic functions

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

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