The Potential Role of Profilin in Metastatic Breast Cancer
نویسنده
چکیده
INTRODUCTION Breast cancer is the most common form of cancer among women. In fact, 1 in 8 women are to be diagnosed with invasive breast cancer, the fatal form of breast cancer. Already in 2016, there have been approximately 250,000 cases of metastatic breast cancer with a death total of around 41,000 women [1]. Clearly, there is a need for better treatment options or detection methods for this form of cancer. The actual deaths, however, are not caused by the breast cancer itself. Rather, it is the spread, or metastasis, of cancer niches from the primary site in the breast to secondary sites such as lung or lymphatic tissue that leads to death [2]. Metastasis is characterized by significant cell migration. Such migration is regulated by the dynamic actin cytoskeleton. Actin, in turn, is regulated by a protein known as profilin (Pfn) which, under normal physiological conditions, helps to sequester free actin monomers and attach them to further actin polymerization [3]. In pathophysiological states, lower levels of profilin have been associated with more aggressive and metastatic breast cancer [4]. However, Pfn, which comes in two isomers: profilin-1 (Pfn1) and profilin-2 (Pfn-2), regulates cancer differently depending on the stage that the disease is in. Our lab has shown that in early stages of cancer, profilin induces the migration of cancer cells to secondary locations; however, once these cells reach the new sites profilin actually impedes the recolonization of a new niche [2]. Clearly, Pfn’s function in cancer is not as cut and dry as other proteins such as Ras or p53. Moreover, E-cadherin is a transmembrane cell-cell connecting protein which has been shown to be a tumor suppressor. Loss of E-cadherin induces what is known as epithelial to mesenchymal transition (EMT) in which cells become unbound from each other and are thus allowed to migrate [4]. EMT is a hallmark of metastatic cancers. Structurally, E-cadherin is anchored to the cell via adaptor proteins that are then attached to actin fibers [5]. Our lab has previously shown that this structural relationship also plays a role with the signaling axis of both profilin and E-cadherin. When Pfn-1 is knocked down via siRNA in MDA-MB-231 breast cancer cells, there is a knockdown of 46% cell-cell connections made through E-cadherin [4].
منابع مشابه
Role of pathologic prognostic factors in breast cancer patients with isolated bone metastasis and relationship between SUVmax and prognostic factors
Introduction: 18F-FDG PET/CT provides very effective results in detecting metastases of breast cancer. In our study, we investigated the relationship between maximum standard uptake value (SUVmax) and prognostic pathologic factors in breast cancer cases with isolated bone metastasis and whether there was any difference in terms of prognostic pathologic factors betwee...
متن کاملThe Role of Matrix Metalloproteinase-3 Functional 5A/6A Promoter Polymorphism in Tumor Cell Progression and Metastasis of Breast Cancer
In the human genome, chromosome 11 contains a cluster of matrix metalloproteinase (MMP) genes. Single nucleotide polymorphisms in the promoter region of MMP genes are important for MMP expression. A common adenine deletion polymorphism (5A) at position -1171 of the MMP-3 gene promoter (5´-AAAAAACCAT-3´ change to 5´-AAAAACCAT-3´) facilitates transcriptional factor binding and MMP-3 promoter acti...
متن کاملInhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics
Objective(s): Various studies have been conducted to reduce the metastatic behavior of cancerous cells. In this regard, ectopic expression of anti-metastatic microRNAs by miR-mimic and miR-restoration-based therapies could bring new insights to the field. In the present study, the consequences of co-transfecting breast cancer cell lines with miR-193b and miR-31 were investigated via invasion an...
متن کاملComparative Analysis of CD4+ and CD8+ T Cells in Tumor Tissues, Lymph Nodes and the Peripheral Blood from Patients with Breast Cancer
Background: CD4+ and CD8+ T cells are the main types of lymphocytes in cell-mediated immunity and play a central role in the induction of efficient immune responses against tumors. The frequencies of T cell subtypes in the peripheral blood and tumor tissues, and draining lymph nodes (dLN) can be considered as useful markers for evaluation of the immune system in cancers. Methods: In this study,...
متن کاملActin Filaments at the Leading Edge of Cancer Cells Are Characterized by a High Mobile Fraction and Turnover Regulation by Profilin I
Cellular motility is the basis for cancer cell invasion and metastasis. In the case of breast cancer, the most common type of cancer among women, metastasis represents the most devastating stage of the disease. The central role of cellular motility in cancer development emphasizes the importance of understanding the specific mechanisms involved in this process. In this context, tumor developmen...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2017