Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.
Adaptor Proteins, Signal Transducing
/ physiology
Adult
Aged
Animals
Breast Neoplasms
/ pathology
Cell Line, Tumor
DNA-Binding Proteins
/ physiology
Disease Progression
Epithelial-Mesenchymal Transition
Female
Humans
Mice
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis
RNA-Binding Proteins
/ physiology
Receptor, EphA3
/ genetics
EPHA3
Sam68
Xenograft
breast cancer
immunohistochemistry
metastasis.
Journal
Current cancer drug targets
ISSN: 1873-5576
Titre abrégé: Curr Cancer Drug Targets
Pays: Netherlands
ID NLM: 101094211
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
01
2019
revised:
08
04
2019
accepted:
28
06
2019
pubmed:
23
8
2019
medline:
11
5
2021
entrez:
22
8
2019
Statut:
ppublish
Résumé
Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer. The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68. Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer. High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.
Sections du résumé
BACKGROUND
Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer.
MATERIALS AND METHODS
The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68.
RESULTS
Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer.
CONCLUSION
High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.
Identifiants
pubmed: 31433759
pii: CCDT-EPUB-99751
doi: 10.2174/1568009619666190718124541
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
DNA-Binding Proteins
0
KHDRBS1 protein, human
0
RNA-Binding Proteins
0
EPHA3 protein, human
EC 2.7.10.1
Receptor, EphA3
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
76-83Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.