Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro

Abstract

Background The human Obg-like ATPase 1 (OLA1) protein has been reported to play an important role in cancer cell proliferation. The molecular mechanism underlying OLA1 regulated oral metastasis is still unknown. We investigated in this study the regulatory role of OLA1 playing in oral squamous cell metastasis. Results A series of in vitro assays were performed in the cells with RNAi-mediated knockdown or overexpression to expound the regulatory function of OLA1 in oral cancer. We found that the endogenous level of OLA1 in a highly metastatic oral squamous cell line was significantly lower than that in low metastatic oral cells as well as in normal oral cells. Escalated expression of OLA1 resulted in a reduced ability of metastasis in highly metastatic cells, and enhanced its sensitivity to the paclitaxel treatment. Further analysis of the EMT markers showed that Snail, Slug, N-cadherin were up-expressed significantly. Meanwhile, E-cadherin was significantly down-regulated in the oral cancer cells with OLA1-knocked down, suggesting that OLA1 inactivated EMT process. Furthermore, we found that OLA1 suppressed oral squamous cell metastasis by suppressing the activity of a TGFβ/SMAD2/EMT pathway. Conclusion Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

“…In hepatocellular carcinoma, downregulation of OLA1 signi cantly inhibited the proliferation, migration, invasion and tumorigenicity of hepatocellular carcinoma cells [15]. On the contrary, recent study on oral carcinoma revealed that knockdown OLA1 enhanced cell migrative ability, but have no effect on cell proliferation [10]. Even in the same type of cancer, the role of OLA1 need to be further explored.…”

“…In breast cancer, escalated expression of OLA1 promoted the EMT process in tumor cells through TGF-β/Smad signaling cascades, resulting in the enhanced expression of antiapoptosis-related proteins and the strengthening depolymerization of microtubules in tumor cells [19]. However, study on oral cancer revealed contrary results that OLA1 regulate EMT process negatively [10]. These data demonstrated that the relationship between OLA1 and EMT may be cancer type-speci c. The present study found that OLA1 expression was positively related with Snail, which is the key positive regulation molecule of EMT, indicating the potential role of OLA1 contributing to EMT in GC.…”

“…In lung cancer, OLA1 contributed to cell epithelial-mesenchymal transition(EMT) and its overexpression was associated with clinical progression and poor survival [9]. Contrarily, in oral cancer, Liu et al reported that OLA1 inactivated EMT process and inhibited cancer cell metastasis [10]. The role of OLA1 in different cancers remains debatable.…”

Knockdown of Obg-like ATPase 1 enhances sorafenib sensitivity by inhibition of GSK-3β/β-catenin signaling in hepatocellular carcinoma cells

“…Moreover, we indicated that knockdown of OLA1 suppressed GSK-3β/ β-catenin signaling activation (Figure 5). Accumulating reports have shown that OLA1 is highly expressed in most cancers, such as HCC and breast cancer (28,38,39). Given the essential functions of OLA1 in stress responses, it is reasonable to suggest that OLA1 may be a potential therapeutic target for cancer.…”

Clinicopathological significance of Obg-like ATPase 1 and its association with Snail in gastric cancer

“…In lung cancer, OLA1 contributes to cell epithelial-mesenchymal transition (EMT), and its overexpression has been associated with clinical progression and poor survival [9]. Conversely, in oral cancer, Liu et al reported that OLA1 inactivated the EMT process and inhibited can-cer cell metastasis [10]. The role of OLA1 in different cancers remains debatable.…”