Cyclin D1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma

Abstract

Cyclin D1, an important regulator of cell cycle, carries out a central role in the pathogenesis of cancer determining uncontrolled cellular proliferation. In normal cells, Cyclin D1 expression levels are strictly regulated, conversely, in cancer, its activity is intensified in various manners. Different studies demonstrate that CCDN1 gene is amplified in several tumor types considering it as a negative prognostic marker of this pathology. Cyclin D1 is known for its role in the nucleus, but recent clinical studies associate the amount located in the cytoplasmic membrane with tumor invasion and metastasis. Cyclin D1 has also other functions: it governs the expression of specific miRNAs and it plays a crucial role in the tumor-stroma interactions potentiating most of the cancer hallmarks. In the present review, we will summarize the current scientific evidences that highlight the involvement of Cyclin D1 in the pathogenesis of different types of cancer, best of all in breast cancer. We will also focus on recent insights regarding the Cyclin D1 as molecular bridge between cell cycle control, adhesion, invasion, and tumor/stroma/immune-system interplay in cancer.

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

“…Cyclin D1 also has CDK independent functions through its binding to histone acetylases, histone deacetylases, and nuclear receptors to regulate cell proliferation, growth, and differentiation. Moreover, it functions in the DNA repair system by binding to RAD51 involved in the homologous recombination of DNA during double strand break repair [ 225 , 226 , 227 , 228 ]. TNBC also display a frequent alteration of RB1 and the DNA damage response gene, BRCA1.…”

Inhibitory effect of Saccharomyces cerevisiae extract obtained through ultrasound-assisted extraction on melanoma cells

“…Several signaling molecules, including p53, MMP7, c-myc, c-Jun, cyclin D1, COX-2, and FRA1 participate in this pathway [39] . Specifically, inhibition of c-myc induces cellular crisis via telomerase dysfunction and oxidative stress [40] , while cyclin D1 has a central role in the pathogenesis of most cancers [41] . Results of the current study indicate that UAEY treatment inhibited melanoma cell proliferation, while reducing the abundance of cyclin D1 and c-myc in vitro , and inhibited melanoma tumor growth and cyclin D1 levels in vivo .…”

CDK4/6 Inhibitors in Melanoma: A Comprehensive Review

“…A critical role in the oncogenic evolution of the p16 ink4A -cyclin D-CDK4/6-RB pathway is played by CCND1, a node where many upstream stimuli converge [27].…”