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The Role of p53-Ninj2 loop in Tumor Progression and Metastasis

Institution: University of California, Davis
Investigator(s): Xinbin Chen,
Award Cycle: 2019 (Cycle 30) Grant #: T30IP0886 Award: $492,239
Subject Area: Cancer
Award Type: High Impact Pilot Award

Initial Award Abstract
Recent studies indicate that cigarette smoke is considered as an important risk factor for breast cancer development and progression. Cigarette smoke contains 70 carcinogens, most of which are known mutagens and capable of activating oncogenes and inactivating tumor suppressor genes, such as TP53, through genetic mutations. Indeed, TP53 is frequently mutated in breast cancer and the rate of p53 mutation is much higher in smokers that that in non-smokers. Thus, understanding the biology of p53 will help reveal the biological pathway that contributes to the pathology of breast cancer. Nerve injury-induced protein 2 (Ninj2), a cell adhesion molecule, is induced in response to nerve injury. Notably, Ninj2 expression is increased in breast cancer. However, it is not clear whether Ninj2 is involved in breast cancer development. To this end, we performed a pilot study and found that Ninj2 is activated by p53 and in turn represses p53 expression in breast cancer cells. We also found that loss of Ninj2 inhibits the growth of breast cancer cells carrying wild-type p53 but promotes the growth of cancer cells carrying a mutant p53. Thus, we hypothesize that the p53-Ninj2 loop plays a critical role in breast cancer development and progression. To test this, we will determine the mechanism by which p53 and Ninj2 are mutually regulated. We will also determine whether the p53-Ninj2 loop can explored as a therapeutic target for breast cancer carrying wild type p53. Successful completion of this project would further our understanding of the p53 biology and most importantly, lay a foundation for development of new therapeutics for breast cancer patients. Moreover, the research findings from this project will be presented at the First-Year Seminars or Quit Tobacco classes at UC Davis. The P.I. will discuss with the general audience about how smoke causes cancer from a scientific point of view. By these means, we hope that we can develop positive attitude to help smokers quit smoking and assist non-smokers to motivate other people, such as family members or friends, to quit smoking.