ROCK1 drives colorectal cancer liver metastasis via PRKCH-mediated bioenergetic reprogramming

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metastasis Research

Background:

• Colorectal cancer (CRC) liver metastasis is a major cause of cancer mortality.
• The molecular mechanisms driving CRC metastasis are not fully understood.

Purpose of the Study:

• To identify key molecular regulators of colorectal cancer liver metastasis.
• To elucidate the signaling pathways involved in CRC metastatic progression.

Main Methods:

• Analysis of patient tumor samples for ROCK1 expression.
• In vitro and in vivo functional assays assessing the role of ROCK1 and PRKCH in CRC cell migration and colonization.
• Transcriptomic profiling to identify downstream effectors.
• Luciferase reporter assays to validate transcription factor binding.

Main Results:

• ROCK1 expression is elevated in liver metastases and promotes CRC cell migration and hepatic colonization.
• ROCK1 regulates epithelial-mesenchymal transition (EMT) markers and controls PRKCH expression.
• PRKCH silencing impairs CRC cell motility and metabolic function; its overexpression rescues these defects.
• The ERK2-CREB1 signaling axis mediates ROCK1-driven PRKCH transcription.

Conclusions:

• A novel ROCK1-ERK2-CREB1-PRKCH signaling pathway drives CRC liver metastasis by coordinating EMT and metabolic reprogramming.
• PRKCH represents a potential therapeutic target for advanced colorectal cancer.