NATURE: Fat1 gene loss increases tumor dryness and metastasis potential

FAT1 gene mutations are frequently detected in a variety of human cancers, especially squamous cell carcinoma (SCCs).
of FAT1 has been associated with poor clinical outcomes and therapeutic resistance.
In skin SCCs induced by a combination of chemical carcinogens 7,12-dimethylbenzene (a) and DMBA and 12-O-14 carbonic acid-13-acetic acid (TPA) (hereinafter referred to as DMBA/TPA), Fat1 mutates in about 20% of cases, similar to the situation in human SCCs.
fat1 gene encodes a primary adhesion protein, and we do not yet know much about the role and molecular mechanisms of FAT1 mutations in controlling tumor occurrence and development.
Recently, researchers published in the journal Nature, using mouse models of skin squamous cell carcinoma and lung tumors, found that the absence of Fat1 accelerates tumor occurrence and malignant progression, and promotes a hybrid transition (EMT) between the upper and intersessional forms.
researchers also found this mixed EMT state in squamous cell carcinoma in people with FAT1 mutations.
that the skin squamous cell carcinoma removed from Fat1 showed an increase in dryness and spontaneous metastasis of the tumor.
further transcription and chromosomal spectrometry, combined with proteomic analysis and process studies, found that the loss of FAT1 function activated the CAMK2-CD44-SRC axis, promoted the expression of YAP1 nuclear transtation and ZEB1, and stimulated the interstate state.
loss of this function will also inferfring EZH2 and promote the expression of SOX2, thus maintaining the skin state.
, a comprehensive analysis of the study found the drug resistance and vulnerability of FAT1-missing tumors, which are important for cancer treatment.
study revealed that in mice and humans with squamous cell carcinoma, the loss of FAT1 function promotes tumor occurrence, progression, invasiveness, dryness and metastasis by inducing mixed EMT states.
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