Mest, short for Mesoderm-specific transcript, has been implicated in various biological processes and disease conditions. It has been associated with pathways like IL-6/JAK/STAT3/Twist-1 in breast cancer and STAT3/Twist-1-mediated EMT in bladder cancer, playing a role in tumorigenicity and metastasis [2,3]. Its loss of imprinting has also been linked to certain cancers through promoter switching [2].

High MEST expression in esophageal squamous cell carcinoma (ESCC) was associated with poor patient survival and promoted cancer invasion and metastasis. Mechanistically, it activates SRCIN1/RASAL1-ERK-snail signaling by interacting with PURA, and miR-449a, which is a direct regulator of MEST, has its promoter hypermethylated leading to MEST upregulation. Systemically delivered miR-449a mimic could suppress tumor metastasis without overt toxicity. Additionally, a compound G699-0288 was found to target the MEST-PURA interaction and significantly inhibit cancer metastasis [1]. In breast and bladder cancers, MEST depletion experiments showed that it is required for promoting cell proliferation, migration, invasion, and EMT [2,3].

In conclusion, Mest is involved in important biological processes related to tumorigenesis and metastasis, especially in cancers such as ESCC, breast, and bladder cancers. Functional studies through gene depletion in these cancer models have revealed its oncogenic roles, highlighting its potential as a therapeutic target for cancer treatment.