Involvement of PI3K/Akt pathway in the inhibition of hepatocarcinoma cell invasion and metastasis induced by SASH1 through downregulating Shh-Gli1 signaling

Sun, Cuiyun; Zhang, Zhihao; He, Ping; Zhou, Yan; Xie, Xuhua

doi:10.1016/j.biocel.2017.06.006

Cited by 36 publications

(25 citation statements)

References 29 publications

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“…This indicates that E-cadherin though regulated by Shh , might as well be under the control of some other upstream signal. A negative correlation between the Shh and E-cadherin nevertheless, was reported during metastasis [ [38] , [39] ]. Further, the Paxillin (Pxn), which is a multifunctional focal adhesion adaptor protein, was found to be upregulated here.…”

Section: Discussionmentioning

confidence: 99%

Exposure to sub-lethal dose of a combination insecticide during early embryogenesis influences the normal patterning of mesoderm resulting in incomplete closure of ventral body wall of chicks of domestic hen

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Exposure to sub-lethal dose of a combination insecticide during early embryogenesis influences the normal patterning of mesoderm resulting in incomplete closure of ventral body wall of chicks of domestic hen

et al. 2018

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“…Inhibition of PI3K can suppress propagation of drug-tolerant gastric cancer cell subpopulations enriched by 5-fluorouracil [ 29 ] and also strengthen their response to multiple chemotherapeutic reagents [ 30 , 31 ]. GLI1- mediated activation of PI3K/AKT pathway was observed in colorectal cancer [ 32 ], ovarian cancer [ 33 ], and hepatocellular carcinoma [ 34 ]. Among GLI1 co-expressed genes in TCGA-STAD, 30 genes were enriched in the PI3K-AKT pathway ( Figures 4 , 5 , genes in red).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer

Jia

et al. 2018

Med Sci Monit

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BackgroundThis study assessed the prognostic value of GLI1 in gastric cancer and analyzed the possible GLI1-related signaling network in chemosensitivity.Material/MethodsBioinformatic data mining was performed by using data in the TCGA-Stomach Cancer (TCGA-STAD) and the Kaplan-Meier plotter. GLI1 co-expressed genes in TCGA-STAD were subjected to KEGG pathway analysis. The genes enriched in the KEGG pathways were further subjected to Protein-Protein Interaction (PPI) analysis.ResultsIn TCGA-STAD, high GLI1 gene/exon expression was associated with significantly worse survival (p=0.016 and 0.0023 respectively). In the Kaplan-Meier plotter, high GLI1 expression was associated with unfavorable overall survival (OS) (HR: 1.68, 95%CI: 1.42–2, p<0.0001) and first progression-free survival (FPS) (HR: 1.72, 95%CI: 1.4–2.11, p<0.0001). In TCGA-STAD, 600 GLI1 co-expressed genes were identified (absolute Pearson’s r ≥0.5). The most significant pathways were pathways in cancer (p=230.0E-12) and the Hedgehog signaling pathway (p=6.9E-9). PI3K-AKT pathway (p=17.0E-9) has the largest proportion of gene enrichment. Some GLI1 co-expressed genes in the PI3K-AKT pathway are central nodes in the PPI network and also play important roles in chemosensitivity of gastric cancer. Nevertheless, the mechanisms underlying their co-expression are still largely unexplored.ConclusionsHigh GLI1 expression is associated with unfavorable OS and FPS in patients with gastric cancer. As a member of the Hedgehog signaling pathway, GLI1 co-expressed genes are also largely enriched in PI3K/AKT pathway in gastric cancer, which is closely related to chemoresistance. The underlying mechanisms are still largely unexplored and need further study.

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“…Reduced expression of SASH1 is associated with aggressive tumor growth, metastasis formation, and poor patient survival. Increasing evidence has shown that different signaling pathways, including PI3K/Akt and TGF-β1, induce morphological cellular changes and alterations in cell migration and invasion consistent with the differential expression of SASH1 [10,11]. Interestingly, several studies have reported that SASH1 plays an important role in promoting tumor cell invasion [10,12].…”

Section: Ivyspringmentioning

confidence: 92%

SASH1 promotes melanin synthesis and migration via suppression of TGF-β1 secretion in melanocytes resulting in pathologic hyperpigmentation

Cui¹,

Shu²,

He³

et al. 2020

Int. J. Biol. Sci.

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Dyschromatosis universalis hereditaria (DUH) is an autosomal dominant pigmentary genodermatosis characterized by the presence of patches of hyperpigmentation and hypopigmented macules distributed over the body, with most cases reported in Asia. DUH is a heterogeneous disease and a small portion of patients carry the ABCB6 variant. In the present study, exome sequencing of four generations of a Chinese family with DUH identified a c.1761C>G (p.Ser587Arg) mutation in exon 15 of SAM and SH3 domain containing 1 (SASH1) that was found to co-segregate in some family members. Immunohistological analysis of biopsy specimens showed that SASH1 was diffusely distributed in all layers of the epidermis, suggesting increased transepithelial migration of melanocytes (MCs). The point mutation c.1761C>G of SASH1 was successfully induced in immortalized human melanocyte (PIG1) cells, which resulted in the downregulation of SASH1 expression. Bioinformatics analysis showed that mutated SASH1 downregulated thrombospondin 1 (THBS1) expression and inactivated transforming growth factor beta 1 (TGF-β1) signaling. TGF-β1 expression by PIG1cells was found to negatively regulate SASH1 protein expression. Transwell migration and wound-healing assays showed an increase in the migration and invasion capabilities of the cells carrying the mutation. Further, SASH1 mutations induced downregulation of melanin content. The study results suggest cross-talking between SASH1-TGF-β1 signaling, demonstrating the proposed MC migration modulation models and affecting melanin trafficking in the epithelium.

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Involvement of PI3K/Akt pathway in the inhibition of hepatocarcinoma cell invasion and metastasis induced by SASH1 through downregulating Shh-Gli1 signaling

Cited by 36 publications

References 29 publications

Exposure to sub-lethal dose of a combination insecticide during early embryogenesis influences the normal patterning of mesoderm resulting in incomplete closure of ventral body wall of chicks of domestic hen

Exposure to sub-lethal dose of a combination insecticide during early embryogenesis influences the normal patterning of mesoderm resulting in incomplete closure of ventral body wall of chicks of domestic hen

Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer

SASH1 promotes melanin synthesis and migration via suppression of TGF-β1 secretion in melanocytes resulting in pathologic hyperpigmentation

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