Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy

Oncogene ◽  
2022 ◽  
Author(s):  
Anthony DiNatale ◽  
Ramanpreet Kaur ◽  
Chen Qian ◽  
Jieyi Zhang ◽  
Michael Marchioli ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1792
Author(s):  
Debashri Manna ◽  
Devanand Sarkar

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.


2012 ◽  
Vol 104 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Toshio Kubo ◽  
Nagio Takigawa ◽  
Masahiro Osawa ◽  
Daijiro Harada ◽  
Takashi Ninomiya ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer Clark ◽  
Jessica Freeman ◽  
Howard Donninger

RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.


2018 ◽  
Vol 25 (4) ◽  
pp. 693-707 ◽  
Author(s):  
Jessy Hasna ◽  
Frédéric Hague ◽  
Lise Rodat-Despoix ◽  
Dirk Geerts ◽  
Catherine Leroy ◽  
...  

2017 ◽  
Vol 13 (5) ◽  
pp. 3014-3024 ◽  
Author(s):  
Linlin Li ◽  
Xiaoyong Wei ◽  
Baofeng Wu ◽  
Yuanli Xiao ◽  
Mingzhu Yin ◽  
...  

2020 ◽  
Author(s):  
Marica Rosaria Ippolito ◽  
Valentino Martis ◽  
Christy Hong ◽  
René Wardenaar ◽  
Johanna Zerbib ◽  
...  

AbstractMitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage, together with mutational burden, might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven genome instability and chemoresistance and might explain why some chemotherapies fail to succeed.


2020 ◽  
Vol 21 (19) ◽  
pp. 7304
Author(s):  
Dimitrios Korentzelos ◽  
Amanda M. Clark ◽  
Alan Wells

Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.


2004 ◽  
Vol 64 (21) ◽  
pp. 7664-7667 ◽  
Author(s):  
Sumanta Goswami ◽  
Weigang Wang ◽  
Jeffrey B. Wyckoff ◽  
John S. Condeelis

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