Overexpression of β1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma

Abstract

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed that overexpression of β1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of β1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that β1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC.

High Expression of Plakoglobin Promotes Metastasis in Invasive Micropapillary Carcinoma of the Breast via Tumor Cluster Formation

“…In our comparison of the clinicopathological features between 451 IMPC and 282 IDC-NST patients, we have demonstrated that the incidence of tumor emboli and metastasis was statistically higher in IMPC patients. Previous studies have observed that the epithelial-mesenchymal transition (EMT) was occurred in IMPC cell clusters and may contribute to the invasion and metastasis of IMPC in clustered form 25-26. Given that the histopathological morphology of IMPC is very similar to intravascular tumor emboli, we speculated that the tumor emboli, which derived from primary lesion, could be associated with the change of adherens junctions in IMPC.…”

Comparison of clinicopathological characteristics and prognosis among patients with pure invasive ductal carcinoma, invasive ductal carcinoma coexisted with invasive micropapillary carcinoma, and invasive ductal carcinoma coexisted with ductal carcinoma in situ

“…Chen et al [ 37 ] suggested that patients with IMPC of the breast had better long-term survival than patients with IDC despite its aggressive clinical characteristics, through a comparison based on a large-population database and case-control analysis. Liu et al [ 38 ] found that the OS and DFS were worse in the IMPC group than in the IDC group, mainly because β1 integrin overexpression contributed to polarity reversal, leading to a poor prognosis. Our data showed that the IDC + IMPC patients had significantly worse DFS and OS compared to those with pure IDC and IDC + DCIS ( P < .001).…”

Integrin, Exosome and Kidney Disease

“…Studies have showed that integrin β1 connects ECM and cytoskeletal protein on one side of the cell, which then forms the basal membrane of cells during polarization, such as epithelial cells and endothelial cells ( Lee and Streuli, 2014 ; Moreno-Layseca et al, 2019 ). Besides, dysregulation of integrin or redistribution have a great impact on cellular apical and basal polarization under injury or cancerization ( Glynne et al, 2001 ; Liu et al, 2018a ).…”