title: Axl as a downstream effector of TGF-β1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma.
abstract: The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-β1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-β1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-β1 level, tumor differentiation, lymph node metastasis, and clinical stage (p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, 465 Zhongshan Road, Dalian, 116027, Liaoning Province, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Gong
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ren
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D054462:p21-Activated Kinases / Q000096:biosynthesis*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; C515903:PAK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D000094963:Axl Receptor Tyrosine Kinase