The role of AP-1 in self-sufficient proliferation and migration of cancer cells and its potential impact on an autocrine/paracrine loop

Abstract

Activating protein-1 (AP-1) family members, especially Fra-1 and c-Jun, are highly expressed in invasive cancers and can mediate enhanced migration and proliferation. The aim of this study was to explore the significance of elevated levels of AP-1 family members under conditions that restrict growth. We observed that invasive MDA-MB-231 cells express high levels of Fra-1, c-Jun, and Jun-D during serum starvation and throughout the cell cycle compared to non-tumorigenic and non-invasive cell lines. We then analyzed Fra-1 levels in additional breast and other cancer cell lines. We found breast and lung cancer cells with higher levels of Fra-1 during serum starvation had relatively higher ability to proliferate and migrate under these conditions. Utilizing a dominant negative construct of AP-1, we demonstrated that proliferation and migration of MDA-MB-231 in the absence of serum requires AP-1 activity. Finally, we observed that MDA-MB-231 cells secrete factors(s) that induce Fra-1 expression and migration in non-tumorigenic and non-metastatic cells and that both the expression of and response to these factors require AP-1 activity. These results suggest the presence of an autocrine/paracrine loop that maintains high Fra-1 levels in aggressive cancer cells, enhancing their proliferative and metastatic ability and affecting neighbors to alter the tumor environment.

Re-expression of SMARCA4/BRG1 in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) promotes an epithelial-like gene signature through an AP-1-dependent mechanism

“…A lentivirus construct containing pINDUCER20-Flag-A-FOS was generated as previously described ( Ibrahim et al, 2018 ). BIN67 pIND20-A-FOS cell lines were generated by lentiviral infection as previously described ( Wei et al, 2014 ) and subsequent selection in G418 containing medium [10% TET-FREE FBS (GeminiBio #100–106) + 800 µg/ml G418 (Gibco #10131035), RPMI-1640] to create mass populations.…”

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

“…The predominant role of activating protein (AP-1) in self-sufficient proliferation and migration was recently reported through an intensive study process carried out by Ibrahim [ 46 ] and his group. They highlighted the effect of Fos and c-Jun proteins, the members of the AP-1 family, and its prevalence in the human breast and lung cancer signaling cascade [ 46 ].…”

“…The predominant role of activating protein (AP-1) in self-sufficient proliferation and migration was recently reported through an intensive study process carried out by Ibrahim [ 46 ] and his group. They highlighted the effect of Fos and c-Jun proteins, the members of the AP-1 family, and its prevalence in the human breast and lung cancer signaling cascade [ 46 ]. Exciting findings of Prassas and Diamandis [ 47 ] showed that the mode of action of CG on Na + /K + -ATPase can alter the function of AP-1 and thus regulate transcriptional gene processes.…”

Transcription Factors in the Development and Pro-Allergic Function of Mast Cells

“…Studies on AP-1 gene knockout mice suggest that members of AP-1 family may regulate distinct genes and therefore exert a variety of biological outcomes (112)(113)(114). Members of AP-1 family have been widely recognized for their role in cell proliferation, survival and apoptotic functions (111,(115)(116)(117).…”