An early history of CCN2/CTGF research: the road to CCN2 via hcs24, ctgf, ecogenin, and regenerin

Abstract

The principal aim of this historical review is to present the processes by which the different aspects of CCN2/CTGF/Hcs24 were discovered by different groups and how much CCN2/CTGF, by being integrated into CCN family, has contributed to the establishment of the basic concepts regarding the role and functions of this new class of proteins. This review should be particularly useful to new investigators who have recently entered this exciting field of study and also provides a good opportunity to acknowledge the input of those individuals who participated in the development of this scientific field.

A CTGF-RUNX2-RANKL Axis in Breast and Prostate Cancer Cells Promotes Tumor Progression in Bone

“…Secretion by tumor cells of soluble factors such as PTHrP that stimulate osteoblasts to upregulate expression of RANKL, the osteoclast differentiation factor, is one of the mechanisms that mediate the tumor-bone interplay. (4,5) The physiological roles of CTGF include skeletogenesis, angiogenesis, and injury repair. This vicious cycle between tumor cells and bone resorption (3) has recently been proposed as a characteristic of the overt metastasis stage.…”

“…(2) In turn, by degrading bone matrix, osteoclasts induce the release of latent growth factors like TGF-β to promote tumor growth, resulting in further secretion of tumor-derived factors. (4,(6)(7)(8)(9) Pathologically, CTGF has been linked to fibrotic diseases and malignancies. (1) Connective tissue growth factor (CTGF), also called CCN2, is a small secreted matrix protein that regulates various cellular functions including proliferation, adhesion, migration, and invasion.…”

“…(1) Connective tissue growth factor (CTGF), also called CCN2, is a small secreted matrix protein that regulates various cellular functions including proliferation, adhesion, migration, and invasion. (4,5) The physiological roles of CTGF include skeletogenesis, angiogenesis, and injury repair. (4,(6)(7)(8)(9) Pathologically, CTGF has been linked to fibrotic diseases and malignancies.…”

“…(4,5) The physiological roles of CTGF include skeletogenesis, angiogenesis, and injury repair. (4,(6)(7)(8)(9) Pathologically, CTGF has been linked to fibrotic diseases and malignancies. (5) Elevated CTGF expression was detected in some types of cancers including breast and pancreatic cancers.…”

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

“…TSK is involved in the regulation of hair cycle, wound healing and bone formation as well (Niimori et al, 2012;Niimori, Kawano, Niimori-Kita, Ihn, & Ohta, 2014;Yano et al, 2017). It also binds in vitro to connective tissue growth factor (CCN2/CTGF) which plays a regulatory role during skeletal development, growth and regeneration by interacting with BMP and TGF-β (Ohta et al, 2019;Takigawa, 2018). During peripheral eye development, TSK directly binds Fzd4 to inhibit Wnt2b binding and ultimately regulates the chicken retinal development (Ohta et al, 2011).…”