These findings not only show the biological efficacy of compound 7e but it is also an effective beginning to explore the mechanism of metastasis and cancer therapy strategy targeting MTA1.
Taken together, these data led us to conclude that the MTA1-S100A4-NMIIA axis exists in endothelial cells as a novel pathway in promoting tumor vascular formation and could be a target for suppressing tumor growth and metastasis.
Metastasis-associated protein 1 (MTA1) is upregulated in multiple malignancies and promotes cancer proliferation and metastasis, but whether and how MTA1 promotes esophageal squamous cell carcinoma (ESCC) tumorigenesis remain unanswered.
Disruption of this prometastatic E2F1:MTA1 interaction reduces hyaluronan synthesis and infiltration of tumor-associated macrophages in the tumor microenvironment, thereby suppressing metastasis.
The expression levels of associated genes, including epithelial cadherin (E‑cadherin), metalloproteinase inhibitor 2 (TIMP‑2), metastasis associated 1 (MTA1) and matrix metallopeptidase 2 (MMP2), were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis and western blotting.
PKD1-mediated downregulation of MTA1 was accompanied by a significant suppression of prostate cancer progression and metastasis in physiologically relevant spontaneous tumour models.
Analysis of 40 cohort studies involving 4564 cancer patients revealed a significant association of MTA1 overexpression with tumor patient age (>50 vs. <50 years: combined OR 0.73, 95% CI 0.57-0.94), tumor grade (G3/4 vs. G1/2: combined OR 1.94, 95% CI 1.48-2.53), tumor size (>3 cm vs. <3 cm: combined OR 2.35, 95% CI 1.73-3.19), T stage (T3/4 vs. T1/2: combined OR 2.11, 95% CI 1.74-2.56), lymph node metastasis (yes vs. no: combined OR 2.92, 95% CI 2.26-3.75), distant metastasis (yes vs. no: combined OR 2.26, 95% CI 1.42-3.59), TNM stage (III/IV vs. I/II: combined OR 2.50, 95% CI 1.84-3.38), vascular invasion (yes vs. no: combined OR 2.26, 95% CI 1.92-3.56), and poor overall survival time (HR 1.83; 95% CI: 1.53-2.20; P = .000).
Overexpression of metastasis-associated protein 1 (MTA1) has been observed in many human malignancies and is significantly related to tumor invasion and metastasis, therapeutic resistance to radiation and chemotherapy, making MTA1 an ideal candidate tumor antigen.
While metastasis-associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown.
Although MTA1 (metastasis-associated 1) has been implicated in breast tumorigenesis and metastasis, its role in endocrine resistance has not been studied.
For endometrial adenocarcinoma cells, laparoscopy, instead of laparotomy, promoted the apoptosis of endometrial adenocarcinoma cells, down-regulated the expression of apoptosis suppressor gene N-myc and metastasis-promoting gene MTA1, up-regulated the expression of apoptosis-promoting gene Fas and metastasis suppressor gene nm23-H1.
It has been suggested that metastasis-associated proteins 1 and 2 (MTA1 and MTA2) are capable of suppressing estrogen receptor alpha (ERα) transactivation activity in breast cancer cells.
Since metastasis tumor antigens (MTAs) MTA1 and MTA2 promote cell proliferation and MTA3 suppresses it, we hypothesized that IUGR alters cell survival/cell death programs driven by placental MTAs.
These findings indicate MTA1 promotes NSCLC cell EMT and metastasis via AKT/GSK3β/β-catenin signaling, which suggests MTA1 may be an effective anti-NSCLC therapeutic target.
In general, downregulation of miR-30e can increase levels of MTA1 in human HCC, and furthermore promote cell invasion and metastasis by promoting ErbB2.
The results indicate that miR-30c-5p, a novel suppressor in tumorigenesis, could inhibit the metastasis and EMT via MTA1, which may offer a possible therapeutic target in GC.