Hsp70 exerts oncogenic activity in the Apc mutant Min mouse model

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Colorectal cancer (CRC) involves the loss of tumor suppressors and gain of proproliferative genes like heat shock protein 70 (Hsp70).
• Hsp70 is overexpressed in CRC, but its role in cancer development versus response to stress is unclear.

Purpose of the Study:

• To investigate the role of Hsp70 in regulating mitogenic signaling pathways during colorectal cancer development.
• To determine if Hsp70 contributes to the transformation process in intestinal epithelial cells.

Main Methods:

• Utilized the Apc (Min/+) mouse model of colorectal cancer.
• Assessed the impact of Hsp70 loss on tumor size, proliferation, cell death, and signaling pathway components (ErbB2, Akt, ERK, β-catenin).

Main Results:

• Loss of Hsp70 significantly reduced tumor size, decreased proliferation, and increased tumor cell death.
• Hsp70 deficiency led to reduced expression of ErbB2, Akt, ERK, and β-catenin, along with diminished β-catenin transcriptional activity.
• Hsp70 stabilizes proteins in receptor tyrosine kinase (RTK) and WNT signaling pathways, which are frequently upregulated in cancers.

Conclusions:

• Hsp70 actively contributes to colorectal cancer development by stabilizing crucial proteins in RTK and WNT signaling pathways, promoting cell proliferation and survival.
• Targeting Hsp70 presents a potential therapeutic strategy for CRC and related cancers, possibly complementing existing treatments like anti-EGFR antibodies.