Journal of Cell Communication and Signaling

, Volume 13, Issue 3, pp 421–434 | Cite as

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

  • Afak Rasheed Salman Zaidi
  • Sadie Dresman
  • Charlotte Burt
  • Simon Rule
  • Lynn McCallumEmail author
Research Article


Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1. Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease with median survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators in progressive MCL. We have used the human MCL cell lines REC1 < G519 < JVM2 as a model for disease aggression. The magnitude of CCN1 expression in human MCL cells is REC1 > G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1 expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expression of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreased with disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1) are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519 cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1 followed a similar profile of expression as cyclin D1. Conversely, p21CIP1 was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellular localization detected p21CIP1/ p27KIP1 primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction with reduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease and treatment resistance.


CCN1 Cyclin D1 CYR61 MCL p21CIP1 p27KIP1 



Mantle cell lymphoma


Non Hodgkin’s Lymphoma


Cyclin D1

CDK4 or 6

Cyclin-dependent kinase 4 (CDK4) or cyclin-dependent kinase 6


Retinoblastoma protein


Ataxia telangiectasia mutated


Cysteine-rich protein 61


Acute myeloid leukaemia


Signal peptide


Insulin like growth factor binding domain


Von Willebrand type C repeat


Thrombospondin type 1 domain


Cysteine rich carboxyl terminal


Heparan sulfate proteoglycans


Bone morphogenetic protein


Transforming growth factor β


Vascular endothelial growth factor


Matrix metalloproteinases


Multiple myeloma


Oesophageal squamous carcinoma


Mitogen-activated protein kinase/extracellular-signal-regulated kinase


Osteoclast activating factors


Osteoblast inhibitors




(Cdk Interacting Protein 1)


(Kinase Inhibitory Protein 1)


(Kinase Inhibitory Protein 2)


Triple negative breast carcinoma


Forkhead box O3


Proliferating cell nuclear antigen


Oral squamous cell carcinoma


Hepatocellular carcinoma


Nuclear Localisation Signal


High-grade ductal carcinoma in situ


Non-small-cell lung cancer



We would like to thank the Iraqi Government for funding this work.


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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.School of Biomedical and Healthcare Science, Peninsula Schools of Medicine and DentistryPlymouth UniversityPlymouthUK
  2. 2.Department of Biology, College of Education for Pure ScienceUniversity of DiyalaBaqubaIraq

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