ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

Molina, Angie; Vélot, Lauriane; Ghouinem, Lydia; Abdelkarim, Mohamed; Bouchet, Benjamin Pierre; Luissint, Anny‐Claude; Bouhlel, Imène; Morel, Marie Hélène; Sapharikas, Elène; Tommaso, Anne Di; Honoré, Stéphane; Braguer, Diane; Gruel, Nadège; Vincent‐Salomon, Anne; Delattre, Olivier; Sigal‐Zafrani, Brigitte; André, Fabrice; Terris, Benoı̂t; Akhmanova, Anna; Benedetto, Mélanie Di; Nahmias, Clara; Rodrigues-Ferreira, Sylvie

doi:10.1158/0008-5472.can-12-3565

Cited by 56 publications

(85 citation statements)

References 36 publications

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“…These results provided strong evidences indicating that MTUS1 was a potential tumor suppressor in gastric cancer. Our data are consistent with previous reports in breast cancer that silencing MTUS1 expression by siRNA facilitated breast cancer cell proliferation by accelerating cell cycle, and also promoted cell motility by regulating microtubule dynamics [27]. Further work will be conducted to illustrate if MTUS1 has a role in regulating tumor-associated angiogenesis or resistance to chemo-therapeutic drugs.…”

Section: Discussionsupporting

confidence: 91%

Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis

Li¹,

Liu²,

Yu³

et al. 2014

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Though the overall incidence of gastric cancer was decreasing in the developed countries in the past decades, it is still a serious threat to human health throughout the world. The molecular mechanisms underlying development of gastric cancer remains unclear. Though accumulating evidences shed a light on the implications of mitochondrial tumor suppressor (MTUS1) in carcinogenesis, the functional role of MTUS1 in regulation of proliferation and metastasis of gastric cancer cell is still poorly understood. In this study, we showed that the level of MTUS1 expression is relatively low in gastric cancer cell lines compared to normal gastric epithelial cells. By using clinical samples, we found that MTUS1 expression is downregulated in tumor tissues compared to non-cancerous counterpart, and loss of MTUS1 was associated with high incidence of lymph node metastasis and poor patient outcome. Moreover, we demonstrate that MTUS1 has a significant impact on both the proliferative and metastatic potential of gastric cancer cell line, which were further supported by using mice tumor xenograft models. The present data suggested MTUS1 as a potential tumor suppressor in gastric cancer and might lead to a better understanding of gastric carcinogenesis.

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Section: Discussionsupporting

confidence: 91%

Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis

Li¹,

Liu²,

Yu³

et al. 2014

neo

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“…The expression or function of other microtubule regulators, such as survivin Rosa et al, 2006), ATIP3 (Molina et al, 2013;Velot et al, 2015) and the +TIPs EB1 (Liu et al, 2009;Stypula-Cyrus et al, 2014) and APC (Etienne-Manneville, 2009), was found to be altered in certain cancers, but the exact role of these proteins in 3D cell migration is still unclear. Mutations in genes encoding tubulin isoforms and different microtubule regulators including +TIPs have also been associated with neurodevelopmental diseases, including disorders of neuronal migration (Breuss and Keays, 2014;Chakraborti et al, 2016;van de Willige et al, 2016), and it will be interesting to investigate which of their functions reflect general mechanisms of 3D cell motility and which are neuron specific.…”

Section: Microtubule Alteration and Diseases Related To Cell Migrationmentioning

confidence: 99%

Microtubules in 3D cell motility

Bouchet

Akhmanova

2017

Journal of Cell Science

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102

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Three-dimensional (3D) cell motility underlies essential processes, such as embryonic development, tissue repair and immune surveillance, and is involved in cancer progression. Although the cytoskeleton is a well-studied regulator of cell migration, most of what we know about its functions originates from studies conducted in twodimensional (2D) cultures. This research established that the microtubule network mediates polarized trafficking and signaling that are crucial for cell shape and movement in 2D. In parallel, developments in light microscopy and 3D cell culture systems progressively allowed to investigate cytoskeletal functions in more physiologically relevant settings. Interestingly, several studies have demonstrated that microtubule involvement in cell morphogenesis and motility can differ in 2D and 3D environments. In this Commentary, we discuss these differences and their relevance for the understanding the role of microtubules in cell migration in vivo. We also provide an overview of microtubule functions that were shown to control cell shape and motility in 3D matrices and discuss how they can be investigated further by using physiologically relevant models.

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“…Moreover, expression of MTUS1 was significantly lower in triple-negative breast cancer (11). Silencing of MTUS1 expression promoted breast cancer cell proliferation, a result further supported in experiments using xenograft models (11,29). In colon cancer, Zuern et al found that silencing of MTUS1 significantly promoted cellular proliferation (12).…”

Section: Kaplan-meier Analysis For Cancer-specific (A) and Disease-mentioning

confidence: 81%

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Sim¹,

Kim²,

Kim³

et al. 2019

In Vivo

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Background/Aim: Microtubule-associated scaffold protein 1 (MTUS1) acts as tumor suppressor in several cancer types. This study assessed the relationship between clinicopathological characteristics and expression of microRNA candidates based on MTUS1 expression in gallbladder cancer (GBC). Materials and Methods: MTUS1 expression was evaluated by immunohistochemical staining of tissue microarrays from 109 cases of GBC. The association of MTUS1 expression with clinicopathological factors was explored. Two microRNA candidates (miR-19a-3p, and miR-19b-3p), which were identified by a literature review and computational analysis, were assessed in GBC tissue samples by quantitative real-time polymerase chain reaction. Results: Low MTUS1 expression in GBC was associated with high histological grade, perineural invasion, lymphovascular invasion, high T-stage, advanced TNM stage, poorer disease-free survival, and poorer cancer-specific survival. No statistical association between MTUS1 expression and expression of microRNA candidates was observed. Conclusion: MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC. Although gallbladder cancer (GBC) is rare, it is the most common malignant tumor of the biliary tract (1-4). No specific symptoms or reliable diagnostic markers are established for GBC. In addition, GBC is diagnosed late; moreover, systemic chemotherapy and radiation therapy do not produce significant improvement in survival or quality of life for patients with GBC (1-3). Thus, patients with GBC do not have a favorable clinical outcome (1-3). Therefore, it is essential to evaluate new biomarkers for predicting the prognosis of patients with GBC. Microtubule-associated scaffold protein 1 (MTUS1), also known as angiotensin II receptor-interacting protein (ATIP), is located on chromosome 8p22 and contains 17 exons (5, 6). MTUS1 acts as a tumor-suppressor gene, exhibiting low expression in a variety of malignancies, including breast, colorectal, head and neck, ovary, stomach, salivary gland, and urinary bladder cancer (7-18). MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by binding target mRNA at the post-transcriptional level. As miRNA pairing targets mRNAs in an imperfect manner, a single miRNA can target multiple genes; and one gene may be affected by multiple miRNAs (1, 19, 20). Recently, Ge et al. demonstrated that miR-19a and miR-19b co-regulate MTUS1 in lung cancer (14). Kara et al. reported decreased MTUS1 expression and elevated miR-183-5p expression in advanced stages of breast cancer (10). Additionally, several miRNAs including miR-135b-5p, miR-373-3p, miR-183-5p, miR-142-5p, miR-200c-3p, and miR-19a-3p, may play important roles in colorectal carcinoma through MTUS1 (21). The role of MTUS1 as a tumor suppressor has been reported, however, the expression of MTUS1 and its clinicopathological significance in GBC has not yet been evaluated. Thus, this study aimed to assess the clinicopathological parameters in association with MTUS1 expr...

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ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

Cited by 56 publications

References 36 publications

Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis

Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis

Microtubules in 3D cell motility

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

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