Standard CD44 modulates YAP1 through a positive feedback loop in hepatocellular carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Hepatology

Background:

• CD44 and YAP are established poor prognostic factors in hepatocellular carcinoma (HCC).
• The mechanistic interplay between CD44 and YAP in HCC tumorigenesis is not well understood.
• Investigating the mutual regulation between CD44 standard (CD44S) and YAP1 is crucial for understanding HCC progression.

Purpose of the Study:

• To elucidate the mutual regulatory relationship between CD44S and YAP1 in HCC.
• To determine the role of CD44S and YAP1 in HCC cell proliferation and invasion.
• To identify potential therapeutic strategies targeting the CD44S-YAP1 axis in HCC.

Main Methods:

• Immunohistochemical staining of CD44S and YAP1 in 40 pairs of HCC tumor and normal tissues.
• In vitro experiments using HCC cell lines to assess the regulation of YAP1 by CD44S.
• Analysis of the YAP1/TEAD axis in regulating CD44S expression.

Main Results:

• High CD44S or YAP1 expression correlated with younger age and worse pathology grade in HCC patients.
• Elevated CD44S and YAP1 levels were associated with increased vascular invasion and liver cirrhosis, respectively.
• A positive correlation was observed between CD44S and YAP1 expression in HCC tissues, indicating a feedback loop.

Conclusions:

• CD44S positively regulates YAP1 expression and its target genes via the PI3K/Akt pathway in HCC.
• CD44S is also regulated by the YAP1/TEAD axis, establishing a positive feedback loop.
• This CD44S-YAP1 feedback loop is a conserved module promoting HCC proliferation and invasion, representing a potential therapeutic target.