MACC1 is involved in the regulation of proliferation, colony formation, invasion ability, cell cycle distribution, apoptosis and tumorigenicity by altering Akt signaling pathway in human osteosarcoma

Abstract

There is mounting evidence that metastasis-associated in colon cancer-1 (MACC1) plays pivotal roles in development and progression of many tumors, particularly in osteosarcoma (OS). However, its precise roles and molecular mechanisms remain to be delineated in OS. In the current study, we found that the levels of MACC1 mRNA and protein in four OS cell lines (MG-63, HOS, SaOS-2 and U2OS) were significantly higher than that in hFOB1.19 osteoblast (P < 0.05). The vector pcDNA-MACC1 contributed to the increase of MACC1 level in MG-63 cells, whereas MACC1 siRNA evoked the decrease of MACC1 level in U2OS cells. In addition, MACC1 downregualtion caused the inhibition of cell proliferation in vitro, colony formation, invasion and tumor growth in vivo, arrested cell cycle in G0/G1 phase and induced cell apoptosis in U2OS cells, and reversed effects were observed in MG-63 cells by MACC1 upregulation. Most notably, MACC1 depletion markedly inactivated Akt signaling pathway in U2OS cells, conversely, MACC1 upregulation evidently activated Akt signaling pathway in MG-63 cells. Collectively, our data presented herein suggest that biological implications triggered by MACC1 may be tightly associated with the status of Akt signaling pathway in OS.

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

“…MACC1, first identified as a colon cancer oncogene, potentially functions as an early diagnosis biomarker and is associated with the progression of multiple solid tumors (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Stein et al (12) demonstrated that MACC1 upregulation was associated with benign-malignant tumor transition.…”

“…Previous studies have suggested that MACC1 is associated with the Akt and Ras/EPH receptor B2 signaling pathways (28)(29)(30). Zhang et al (28) demonstrated that MACC1 expression may affect the PI3K/Akt signaling pathway and the protein expression of matrix metallopeptidase (MMP)2 and MMP9.…”

“…Zhang et al (28) demonstrated that MACC1 expression may affect the PI3K/Akt signaling pathway and the protein expression of matrix metallopeptidase (MMP)2 and MMP9. Meng et al (30) revealed that pAkt was a key target gene of MACC1, and that pAkt expression was significantly suppressed by MACC1 downregulation in nasopharyngeal carcinoma cells.…”

Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells

“…Previous studies have identified several candidate gene targets for osteosarcoma gene therapy (12)(13)(14). For example, the proliferation inhibition of osteosarcoma U2OS cells has been associated with the repression of G 1 /S cell cycle transition mediated by the overexpression of connexin43 (12).…”

“…Knockdown of S100 calcium binding protein A4 is correlated with the reduced proliferation and invasiveness of osteosarcoma MG-63 cells (13). Following the loss of MACC1 MET transcriptional regulator, osteosarcoma cells were demonstrated to be less proliferative and more apoptotic, and exhibited lower colony-forming and invasive abilities (14). However, there are only a few potential therapeutic targets for osteosarcoma, thus the identification of novel candidate genes is warranted to provide more viable clinical therapeutic strategies for the treatment of the disease.…”