p20BAP31 promotes cell apoptosis via interaction with GRP78 and activating the PERK pathway in colorectal cancer

Area of Science:

• Molecular Biology
• Cancer Research
• Cellular Stress Response

Background:

• Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide.
• Current CRC treatments face limitations, necessitating the identification of novel therapeutic targets.
• The protein p20BAP31 shows promise for CRC treatment due to its ability to induce apoptosis.

Purpose of the Study:

• To comprehensively explore the molecular functions of p20BAP31 in the context of colorectal cancer.
• To investigate the role of p20BAP31 in endoplasmic reticulum (ER) stress and its impact on tumor growth.
• To elucidate the underlying mechanisms by which p20BAP31 exerts its anti-tumor effects.

Main Methods:

• Investigated the localization and effects of exogenous p20BAP31 in CRC cells.
• Analyzed the activation of the unfolded protein response (UPR) via the PERK pathway.
• Examined the role of p20BAP31 in reactive oxygen species (ROS) accumulation and apoptosis.
• Performed mechanistic studies involving GRP78 binding, HSF1 translocation, and promoter activity.

Main Results:

• Exogenous p20BAP31 localizes to the ER and activates the UPR through the PERK pathway.
• p20BAP31 induces ROS accumulation and apoptosis, significantly attenuating tumor cell growth in vivo.
• p20BAP31 competitively binds GRP78, leading to hyperactivation of the UPR.
• p20BAP31 upregulates GRP78 expression by promoting HSF1 nuclear translocation and promoter binding.

Conclusions:

• p20BAP31 acts as a novel regulator of ER stress, inducing apoptosis and inhibiting tumor growth in colorectal cancer.
• The findings reveal a mechanism where p20BAP31 modulates ER-mitochondria signaling.
• p20BAP31 represents a potential therapeutic target for anti-tumor strategies in CRC.