Microtubule-associated tumor suppressors as prognostic biomarkers in breast cancer

Abstract

Breast cancer is the most common malignancy in women worldwide. Although important therapeutic progress was achieved over the past decade, this disease remains a public health problem. In the light of precision medicine, the identification of new prognostic biomarkers in breast cancer is urgently needed to stratify populations of patients with poor clinical outcome who may benefit from new personalized therapies. The microtubule cytoskeleton plays a pivotal role in essential cellular functions and is an interesting target for cancer therapy. Microtubule assembly and dynamics are regulated by a wide range of microtubule-associated proteins (MAPs), some of which have oncogenic or tumor suppressors effects in breast cancer. This review covers current knowledge on microtubule-associated tumor suppressors (MATS) in breast cancer and their potential value as prognostic biomarkers. We present recent studies showing that combinatorial expression of ATIP3 and EB1, two microtubule-associated biomarkers with tumor suppressor and oncogenic effects, respectively, improves breast cancer prognosis compared to each biomarker alone. These findings are discussed regarding the increasing complexity of protein networks composed of MAPs that coordinate microtubule dynamics and functions. Further studies are warranted to evaluate the prognostic value of combined expression of different MATS and their interacting partners in breast cancer.

ATIP3 deficiency facilitates intracellular accumulation of paclitaxel to reduce cancer cell migration and lymph node metastasis in breast cancer patients

“…Together these data support a mechanism by which ATIP3 deficiency may induce a conformational change of growing microtubule ends to facilitate paclitaxel binding to the lattice, thereby sensitizing cancer cells to the anti-migratory effects of low doses of chemotherapy. This raises the interesting possibility that high levels of EB1 in ATIP3-low breast tumors may be associated with higher sensitivity to anti-migratory effects of paclitaxel, in line with our recent studies showing that combinatorial expression of ATIP3 and EB1 is a prognostic biomarker of breast cancer patient survival 29,30 .…”

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

“…Functional studies mentioned above [ 49 , 50 ] showing that ATIP3 antagonizes the effects of EB1 on microtubule dynamics, raised the possibility that tumors with low ATIP3 and high EB1 levels may be associated with increased malignancy and worse prognosis compared with other breast tumors. Studies conducted on 5 independent cohorts of breast cancer patients indeed confirmed the increased prognostic value of combined ATIP3/EB1 expression compared with each biomarker alone [ 22 , 70 ].…”

Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

“…In adherent MDA-MB-231 cells grown on the RPM for 24–72 h microtubules were disorganized, with a more evident thickening in perinuclear position, whereas in MCS cells, the tubulin network was completely disrupted showing a slight diffuse fluorescence throughout the entire cytoplasm [ 49 ]. Considering that microtubule-associated tumor suppressors (such as breast cancer 1, BRCA1) can have major impact on cancer aggressiveness and clinical outcome [ 75 ], microtubule rearrangement through s-µ g can indeed be a tool to influence the latter.…”