SOX4 promotes the growth and metastasis of breast cancer

Abstract

Purpose Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo. Methods We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. Results SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. Conclusions SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

LINC00662 enhances cell progression and stemness in breast cancer by MiR-144-3p/SOX2 axis

“…Next, we probed into the downstream mRNA of miR-144-3p. Previous studies verified that SOX2 , SOX4 , OCT4 , and Nanog are involved in cell migration, invasion and stemness [ 26 , 27 ]. Thus, we conjectured that miR-144-3p may mediate cell migration, invasion and stemness via targeting the above genes.…”

“…Soft agar was applied in assays as previously described [ 27 ]. Briefly, transfected cells (500 cells/well) were inoculated into 6-well plates.…”

Decoding molecular programs in melanoma brain metastases

“…15b). Among them were SOX4, a master-regulator of EMT 112, 113 and PTPRZ1 a mediator of stemness in glioblastoma 114 . As both cell lines were unrelated and comprised different sets of mutations (T2002, BRAF/NRAS wt ; BMC1-M1, BRAF V600E ), the CD271-associated regulation of genes was probably context independent.…”

Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway

“…Sox4 could induce tumorigenesis by endowing cancer cells with survivability, mobility, and invasiveness [ 48 ]. Several researches verified that Sox4 is a critical oncogene that is highly expressed in cancers, including prostate cancer [ 49 ], colorectal cancer [ 50 ], bladder cancer [ 51 ], and breast cancer [ 52 ], etc. Sox4 has also been testified to be associated with differentiation, metastasis, and chemoradioresistance in OSCC [ 53 , 54 ].…”