Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer

Abstract

Breast cancer is the leading cause of death by malignancy among women worldwide. Clinical data and molecular characteristics of breast tumors are essential to guide clinician’s therapeutic decisions. In the new era of precision medicine, that aims at personalizing the treatment for each patient, there is urgent need to identify robust companion biomarkers for new targeted therapies. This review focuses on ATIP3, a potent anti-cancer protein encoded by candidate tumor suppressor gene MTUS1, whose expression levels are markedly down-regulated in breast cancer. ATIP3 is a microtubule-associated protein identified both as a prognostic biomarker of patient survival and a predictive biomarker of breast tumors response to taxane-based chemotherapy. We present here recent studies pointing out ATIP3 as an emerging anti-cancer protein and a potential companion biomarker to be combined with future personalized therapy against ATIP3-deficient breast cancer.

Identifying the genes impacted by cell proliferation in proteomics and transcriptomics studies

“…In breast cancer, ATIP3 was found significantly downregulated in taxane-sensitive tumors [ 28 ]. It is an interesting therapeutic target for breast cancer [ 29 ]. Caspase 2 ( CASP2 ) has been shown to cleave the Microtubule-associated protein tau (coded by the gene MAPT ) that promotes microtubule assembly and stability and potentially competes with taxanes for microtubule binding.…”

Delineating the conformational landscape and intrinsic properties of the angiotensin II type 2 receptor using a computational study

“…Several ATIPs have been discovered to interact with the H8 and C-terminal of active AT 2 R [71] , [72] . From the conformational ensemble of AT 2 R, the interface for AT 2 R and ATIP is hidden in the TM bundle center in the inactive state, preventing AT 2 R from interactions.…”

The Angiotensin AT2Receptor: From a Binding Site to a Novel Therapeutic Target

“…Such mechanisms may involve binding to and activation of Src homology region 2 domain-containing phosphatase-1 (SHP-1) (Li J-M et al, 2007), although others suggested that the antiproliferative effect of AT 2 R/ATIP1 is mediated through ATIP1/PPARc binding and crosstalk (Kukida et al, 2016;L€ utzen et al, 2017). Recently, research has focused mainly on ATIP3, which seems to be the main isoform possessing tumor-suppressor properties through interference with microtubule depolymerization within the mitotic spindle apparatus (Haykal et al, 2021). It is currently unclear whether the AT 2 R plays any role in these anticancer effects of ATIP3 or, for that matter, ATIP1.…”

“…The anticancer effects of ATIP3 are reviewed in more detail in Section VI.H and in other reviews (Bozgeyik et al, 2017;Haykal et al, 2021).…”