The intricate mechanism through which UMODL1 accelerating tumor proliferation of Her-2 positive breast cancer as well as trastuzumab resistance

Abstr act： Human epidermal growth factor receptor 2 positive breast cancer is characterized by the overexpression of the Her-2 receptor, rapid tumor growth, strong invasion ability, and high resistance to chemotherapy. Targeted drug therapies for this subtype include trastuzumab and pertuzumab; however, some patients still show resistance to these treatments. The Uromodulin-1-like (UMODL1) gene, also known as Olfactorin, has been identified as a prognostic indicator for survival in patients with esophageal squamous cell carcinoma, lung adenocarcinoma, and colorectal cancer. UMODL1 expression is increased in both Her-2 positive breast cancer cell lines and trastuzumab-resistant cell lines. Elevated UMODL1 promotes the proliferation and migration of breast cancer cells while reducing apoptosis; on the contrary, suppressed UMODL1 has opposite effects. UMODL1 upregulates the expression of Her-2 and binds with Her-2 heterodimers to activate downstream signaling pathways associated with Her-2 activation. This mechanism contributes to the development and progression of Her-2-positive breast cancer while also affecting trastuzumab resistance. In summary, these findings indicate that UMODL1 can serve as a prognostic indicator of survival in patients with Her-2 positive breast cancer while providing guidance on the use of trastuzumab.