Gene Dev: Tsinghua Medical School Zheng Qiball and others reveal key factors that inhibit breast cancer metastasis.

According to the 2018 International Agency for Research on Cancer (IARC) survey, breast cancer has a global incidence rate of 24.2% among women, ranking first among women, of which 52.9% occur in developing countries.
age, the incidence of breast cancer from the age of 20 began to gradually rise, 45 to 50 years of age peak.
, the incidence of breast cancer in China is increasing year by year, more than 300,000 women are diagnosed with breast cancer every year, in the eastern coastal areas and economically developed cities, the incidence of breast cancer increased particularly significantly.
Although the overall survival rate of breast cancer is high, TNBC, which accounts for about 15% of all breast cancers, is still a difficult problem for cancer treatment, known as "three yin" because the three main therapeutic targets of estrogen, progesterone and HER-2 are negative.
breast cancer is considered "the most toxic and dangerous" because of its lack of treatment targets and high risk of recurrence and metastasis.
recently, Zheng Shakeball Laboratory of Tsinghua University School of Medicine, in cooperation with Kang Yibin Laboratory of the Department of Molecular Biology of Princeton University in the United States, published a research paper entitled: ASB13 Asb13 Resmned Breast Cancer Metastasis through Promoting SNAI2 Stage and Repelling Its Transcriptal Repression of YAP online.
the study found the key E3 ubiganic connective enzyme ASB13 that specific to ubibin and degrades the endogenetic SNAI2 protein and found its downstream signaling path.
provides a new target and research direction for inhibiting the metastasis of triple negative breast cancer.
less to get, more to bewildered "less to get, more to bewildered" - from Laozi's Book of Morals.
the millennium famous sentence full of philosophical thought, its core gradually evolved into not greedy, the pursuit of balance of things, but also become a Chinese of the code of conduct.
in highly evolved mammalian cells, the Ubiquitin and proteasome degradation systems (UPS) are key protein machines that maintain a balance of expression among proteins.
when a particular protein molecule is modified by multiple ubiquitin molecules to form a ubiquitin chain, the protein is captured by the protease complex in the cell and degraded to polypeptides and amino acids.
cells have about 1000 kinds of E3 ubilin connective enzymes to control the ubibinization and degradation of different protein molecules, and specific protein substrates can usually only be identified and ubirinized by a few ubiganic connective enzymes, thus achieving the specificity and regulation of protein ubilin degradation.
SNAI2 protein SNAI2 protein is an important member of the SNAIL transcription factor family.
in the initial study of embryonic development, it was found that it plays an important role in cell morphological changes and cell migration in key stages of development.
Subsequent studies found that tumor cells from the endocystic source were able to obtain strong tissue immersion and migration capabilities only by altering the transcription factor represented by SNAI2, changing themselves to a "narrow length" shape similar to fibroblasts, and removing adhesion between cells, thus helping tumor cells to leave in-place tissue and eventually metastasize cancer.
in patients with the worst prognostic triple-negative breast cancer, SNAI2 protein expression levels were significantly higher than those of a variety of breast cancer subtypes that were less prone to metastasis, including estrogen receptor-positive (Estrogen Receptor plus) cancer subtypes.
mechanism of increasing the expression level of SNAI2 protein in triple-yin breast cancer, as well as its endotopic ubiquitin regulation mechanism, is still unclear.
ASB13 inhibits cancer metastasis by ubibinic degradation of SNAI2 and relieves SNAI2 transcription inhibition of YAP through a total ubiganic connective enzyme group screening, current research has found that ASB13 is a key ubibin connective enzyme for ubibinization and promoting endogenetic SNAI2 protein degradation.
and SNAI2, as a transcription factor, is able to bind to the initiator sequence of the YAP gene and inhibit the transcriptional expression of its mRNA.
ASB13 degrades SNAI2 by ubibination, which relieves SNAI2's transcriptional inhibition of YAP and ultimately inhibits cancer metastasis.
team first used a dual fluorescence reporting system to systematically knock down the genome-wide ubiquitin connective enzyme and found that the ubiquitin connective enzyme ASB13 effectively ubiquitinized the degradation of the SNAI2 protein, thereby inhibiting cell migration of breast cancer and cancer metastasis in mice.
further studies have found that the knock-out of ASB13 can cause an increase in the endo-source SNAI2 protein, which in turn inhibits transcriptional expression of the YAP gene in the Hippo signaling path.
is also the first time that the SNAI2 protein has been found to be able to transcription to suppress YAP expression levels.
ASB13 inhibits the transcription inhibition and increases the expression level of YAP by promoting the ubibination and degradation of SNAI2, thereby inhibiting the metastasis of cancer.
ASB13 inhibits the mechanism of tumor metastasis In addition, clinical data analysis also shows that the expression level of ASB13 in triple-negative breast cancer is significantly lower than its expression level in other breast cancer subtypes, thus providing an important molecular mechanism explanation for the high expression of SNAI2 protein in triple-yin breast cancer.
the disclosure of molecular mechanisms in the occurrence and metastasis of SNAI2 and its downstream Hippo signaling path, providing a solid foundation and consideration for future targeted treatments for SNAI2 and YAP path paths.
the snail shell implies the SNAI2 protein, and the hippo implies the YAP protein in the Hippo signaling path.
current studies have shown that SNIA2 inhibits transcriptional expression of YAP, a key factor in the Hippo signaling path.
the first time the SNAIL protein family has been connected to Hippo-YAP's signal regulation network.
, Zheng Shakeball, a researcher at Tsinghua University School of Medicine, and Professor Kang Yibin of Princeton University's Department of Molecular Biology are co-authors of this paper.
, a doctoral student at Tsinghua University School of Medicine, is the first author of this paper.
project has been supported by the National Natural Science Foundation of China, tsinghua-North University Life Center and Tsinghua University School of Medicine and other related funds and institutions.
also received the U.S. Department of Defense Research Fund (BC123187 to Y.K.), the National Institutes of Health (R01CA141062 to Y.K.) support from relevant funds and institutions.
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