TY - JOUR
T1 - Teaming up for trouble
T2 - Cancer cells, transforming growth factor-β1 signaling and the epigenetic corruption of stromal naïve fibroblasts
AU - Lamprecht, Sergio
AU - Sigal-Batikoff, Ina
AU - Shany, Shraga
AU - Abu-Freha, Naim
AU - Ling, Eduard
AU - Delinasios, George J.
AU - Moyal-Atias, Keren
AU - Delinasios, John G.
AU - Fich, Alexander
N1 - Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - It is well recognized that cancer cells subvert the phenotype of stromal naïve fibroblasts and instruct the neighboring cells to sustain their growth agenda. The mechanisms underpinning the switch of fibroblasts to cancer-associated fibroblasts (CAFs) are the focus of intense investigation. One of the most significant hallmarks of the biological identity of CAFs is that their tumor-promoting phenotype is stably maintained during in vitro and ex vivo propagation without the continual interaction with the adjacent cancer cells. In this review, we discuss robust evidence showing that the master cytokine Transforming Growth Factor-β1 (TGFβ-1) is a prime mover in reshaping, via epigenetic switches, the phenotype of stromal fibroblasts to a durable state. We also examine, in detail, the pervasive involvement of TGFβ-1 signaling from both cancer cells and CAFs in fostering cancer development, taking colorectal cancer (CRC) as a paradigm of human neoplasia. Finally, we review the stroma-centric anticancer therapeutic approach focused on CAFs—the most abundant cell population of the tumor microenvironment (TME)—as target cells.
AB - It is well recognized that cancer cells subvert the phenotype of stromal naïve fibroblasts and instruct the neighboring cells to sustain their growth agenda. The mechanisms underpinning the switch of fibroblasts to cancer-associated fibroblasts (CAFs) are the focus of intense investigation. One of the most significant hallmarks of the biological identity of CAFs is that their tumor-promoting phenotype is stably maintained during in vitro and ex vivo propagation without the continual interaction with the adjacent cancer cells. In this review, we discuss robust evidence showing that the master cytokine Transforming Growth Factor-β1 (TGFβ-1) is a prime mover in reshaping, via epigenetic switches, the phenotype of stromal fibroblasts to a durable state. We also examine, in detail, the pervasive involvement of TGFβ-1 signaling from both cancer cells and CAFs in fostering cancer development, taking colorectal cancer (CRC) as a paradigm of human neoplasia. Finally, we review the stroma-centric anticancer therapeutic approach focused on CAFs—the most abundant cell population of the tumor microenvironment (TME)—as target cells.
KW - Cancer
KW - Cancer-associated fibroblasts
KW - Colorectal cancer
KW - Epigenetics
KW - Transforming growth factor-β
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85042677855&partnerID=8YFLogxK
U2 - 10.3390/cancers10030061
DO - 10.3390/cancers10030061
M3 - Review article
AN - SCOPUS:85042677855
SN - 2072-6694
VL - 10
JO - Cancers
JF - Cancers
IS - 3
M1 - 61
ER -
