The MRTF-A/B function as oncogenes in pancreatic cancer

Abstract

Despite evidence that MRTF-A/B, co-activators of serum response factor (SRF), promotes tumor cell invasion and metastasis in cancer, there are no studies describing MRTF-A/B in pancreatic cancer. To clarify involvement of MRTF-A/B expression in pancreatic cancer, we used quantitative reverse transcription-polymerase chain reaction and western blot analysis to detect MRTF-A/B in pancreatic cancer, intraductal papillary mucinous neoplasm (IPMN) and non-neoplastic pancreata. MRTF-A/B expression differs significantly between cancer and non-neoplastic tissues as well as between non-neoplastic tissues and IPMN bulk tissues. Next, we studied the roles of MRTF-A/B in vitro. Overexpression of MRTF-A/B promoted epithelial-mesenchymal transition (EMT) and generated stem cell-like cells in normal pancreatic cells. We performed quantitative reverse transcription-polymerase chain reaction to detect the level of MRTF-A/B in 19 pancreatic cancer cell lines. We found that their expression was associated with gemcitabine resistance. Like in normal pancreatic cells, MRTF-A/B also promoted EMT and promoted formation of stem cell-like cells in pancreatic cancer and they could regulate microRNA expression associated with EMT and CICs. Finally, to further demonstrate the roles of MRTF-A/B in vivo, we performed nude mouse model of s.c. xenograft and found that overexpression of MRTF-A and MRTF-B promoted pancreatic cancer growth. Elucidating the roles of MRTF-A/B will help us to further understand molecular basis of the disease and offer new gene targets for effective therapies.

SRF'ing and SAP'ing – the role of MRTF proteins in cell migration

“…Given that actin polymerization, activity of Rho-GTPases, such as Rac, as well as expression of surface integrins, are all sensitive to perturbations of the redox state (Nimnual et al, 2003;Yan and Smith, 2000), MRTF might impact on cell migration through modulation of the redox state of the cell. Finally, MRTF isoforms have also been shown to regulate the expression of several microRNAs that are involved in cell migration, including miR200, miR96, miR21, as well as miR143 and miR145, to name a few (Davis-Dusenbery et al, 2011;Li et al, 2017;Song et al, 2016). Thus, the regulation of the expression of certain noncoding RNAs is another mechanism of MRTF-mediated control of cell migration that benefits from further investigation.…”

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini

“…These results raise the possibility that elevated MRTF activity leads to a cellular dedifferentiation process, which contributes to the loss of mammary epithelial architecture. Recently, an oncogenic function of MRTF-A/B in normal pancreatic cells was reported, caused by increased stem cell formation and promotion of EMT [45]. MRTF-A has also frequently been implicated in transforming growth factor (TGF)β1-induced EMT and myofibroblast transition [19, 46].…”

L1CAM promotes epithelial to mesenchymal transition and formation of cancer initiating cells in human endometrial cancer

“…It was performed as described previously ( 30 ). Cells (10 3 /ml) in serum-free RPMI1640/1 mM Na-pyruvate were seeded on 0.5% agar precoated 6-well plates.…”