Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Title: Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Radhika Gogoi
* ORCID logo ,
Sandra Galoforo
,
Alexandra Fox
,
Colton Morris
,
Harry Ramos
,
Vir Gogoi
,
Hussein Chehade
,
Nicholas K. Adzibolosu
ORCID logo ,
Chenjun Shi
,
Jitao Zhang
,
Roslyn Tedja
ORCID logo ,
Robert Morris
,
Ayesha B. Alvero
,
Gil Mor
* ORCID logo
Version 1 : Received: 28 August 2023 / Approved: 29 August 2023 / Online: 30 August 2023 (07:10:00 CEST)

A peer-reviewed article of this Preprint also exists.

Gogoi, R.P.; Galoforo, S.; Fox, A.; Morris, C.; Ramos, H.; Gogoi, V.K.; Chehade, H.; Adzibolosu, N.K.; Shi, C.; Zhang, J.; Tedja, R.; Morris, R.; Alvero, A.B.; Mor, G. A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype. Cancers 2023, 15, 4834. Gogoi, R.P.; Galoforo, S.; Fox, A.; Morris, C.; Ramos, H.; Gogoi, V.K.; Chehade, H.; Adzibolosu, N.K.; Shi, C.; Zhang, J.; Tedja, R.; Morris, R.; Alvero, A.B.; Mor, G. A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype. Cancers 2023, 15, 4834.

Abstract

Background: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between epithelial and mesenchymal stage is essential for tissue homeo-stasis. Many of the genes promoting mesenchymal transformation has been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify genes responsible for maintaining the epithelial phenotype and in-hibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expres-sion was determined by qPCR and Western blot analysis. Knockout of CTGF was done using the CTGF sgRNA CRISPR/CAS9. Tumorigenic potential was determined using NCG mice. Results: Knocked-out of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as Anoikis resistance, cytoskel-eton remodeling, increased cell stiffness, and acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for conserva-tion of epithelial structure and function. These findings provide a new window to understand the early stages on mesenchymal transformation

Keywords

epithelial-mesenchymal transition; cytoskeleton; extracellular matrix remodeling; ovarian cancer; anoikis resistance; metastasis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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