Silencing of semaphorin 3C suppresses cell proliferation and migration in MCF‑7 breast cancer cells

Zhu, Xiaofang; Zhang, Xiangjian; Ye, Zhiqiang; Chen, Yizuo; Lv, Lin; Zhang, Xiao‐Hua; Hu, Hongye

doi:10.3892/ol.2017.6920

Cited by 13 publications

(12 citation statements)

References 22 publications

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“…To our knowledge, with the exception of SEMA3G, all SEMA3 family members have been at least partially studied in breast cancer. Most members showed tumour inhibiting roles while only SEMA3E was found to promote tumour invasion and metastasis [13,15,20,[35][36][37][38][39][40][41][42][43][44]. However, as mentioned above, most of the studies were conducted in cell lines or animal models.…”

Section: Sema3 Gene Family In Breast Cancermentioning

confidence: 99%

A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer

Zhang

Klamer

et al. 2020

BMC Med Genomics

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Background: Initially characterized as axon guidance factors, semaphorins also have been implicated to have critical roles in multiple physiological and developmental functions, including the regulation of immune responses, angiogenesis, organ formation, and the etiology of multiple forms of cancer. Moreover, their contribution in immunity and the regulation of tumour microenvironment is becoming increasingly recognized. Here, we provide a comprehensive analysis of class-3 semaphorins, the only secreted family of genes among veterbrate semaphorins, in terms of their expression profiles and their association with patient survival. We also relate their role with immune subtypes, tumour microenvironment, and drug sensitivity using a pan-cancer study. Results: Expression profiles of class-3 semaphorins (SEMA3s) and their association with patient survival and tumour microenvironment were studied in 31 cancer types using the TCGA pan-cancer data. The expression of SEMA3 family varies in different cancer types with striking inter-and intra-cancer heterogeneity. In general, our results show that SEMA3A, SEMA3C, and SEMA3F are primarily upregulated in cancer cells, while the rest of SEMA3s are mainly down-regulated in the tested tumours. The expression of SEMA3 family members was frequently associated with patient overall survival. However, the direction of the association varied with regards to the particular SEMA3 isoform queried and the specific cancer type tested. More specifically, SEMA3A and SEMA3E primarily associate with a poor prognosis of survival, while SEMA3G typically associates with survival advantage. The rest of SEMA3s show either survival advantage or disadvantage dependent on cancer type. In addition, all SEMA3 genes show significant association with immune infiltrate subtypes, and they also correlate with level of stromal cell infiltration and tumour cell stemness with various degrees. Finally, our study revealed that SEMA3 genes, especially SEMA3C and SEMA3F may contribute to drug induced cancer cell resistance. Conclusions: Our systematic analysis of class-3 semaphorin gene expression and their association with immune infiltrates, tumour microenvironment and cancer patient outcomes highlights the need to study each SEMA3 member as a separate entity within each specific cancer type. Also our study validated the identification of class-3 semaphorin signals as promising therapeutic targets in cancer although further laboratory validation still needed.

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Section: Sema3 Gene Family In Breast Cancermentioning

confidence: 99%

A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer

Zhang

Klamer

et al. 2020

BMC Med Genomics

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“…Also, SEMA3C is highly upregulated and oncogenic in various types of cancers, including glioblastoma, prostate cancer, and breast cancer. Studies have revealed that SEMA3C promotes tumor cell proliferation, epithelial-to-mesenchymal transition, or sustains cancer stemness [14,[22][23][24][25]. Because PKD epithelial cells have similar properties to cancer cells such as sustained proliferative and inflammatory signaling [26], it is as- Fig.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells

Kim

et al. 2020

Am J Nephrol

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Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner. Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion. Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation. Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.

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“…However, it is unclear if the R745A mutant is able to interact with the receptor neuropilin and if it is still able to activate signaling pathways (e.g., VEGFR and Rac1 activation pathways) within the cells. Zhu and coauthors demonstrated that the knockdown of SEMA3C significantly inhibited breast cancer cell MCF-7 growth and migration ( 20 ); therefore, it would be interesting to examine how the Sema3C R745A mutant affects the endothelial cell migration process. These studies would help to disclose the significance of the Sema3C protein furin cleavage site 742 RNRR 745 in molecular processes.…”

Section: Discussionmentioning

confidence: 99%

Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro

Valiulytė

Preitakaite

Tamašauskas

et al. 2018

Braz J Med Biol Res

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Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein. Several studies have shown that the furin-mediated processing of the basic domain of Sema3F and Sema3A is critical for association with receptors. It is unclear, however, if this mechanism can also be applied to other Sema3 proteins, including the main subject of this study, Sema3C. To address this question, we generated a variant of the full-length human Sema3C carrying point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745, which would disable the processing of Sema3C at this specific location. The effects produced by this mutation were tested in an in vitro angiogenesis assay together with the wild-type Sema3C, Sema3A, and Sema3F proteins. Our results showed that the inhibitory effect of Sema3C on microcapillary formation by human umbilical vein endothelial cells could be abrogated upon mutation at the Sema3C basic domain within putative furin cleavage site 742RNRR745, indicating that this site was essential for the Sema3 biological activity.

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Silencing of semaphorin 3C suppresses cell proliferation and migration in MCF‑7 breast cancer cells

Cited by 13 publications

References 22 publications

A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer

A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer

Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells

Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro

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