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Cancers
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Multiple Signaling Pathways in Ovarian Cancer
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Multiple Signaling Pathways in Ovarian Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 4604

Special Issue Editor

Dr. Gil Mor

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI 48201, USA
Interests: ovarian cancer; epithelial mesenchymal transition; immune modulation; immune therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Ovarian cancer is the fourth leading cause of cancer-related death in women in the United States and is the leading cause of gynecological cancer death. The high rate of mortality reflects the poorly understood preclinical state of ovarian cancer and the lack of specific symptoms. 

Approximately 80% of patients with primary disease respond to surgery and chemotherapy; however, the number of responders decreases to ~15% for recurrent cancers. Individuals who succumb to advanced-stage ovarian cancer inevitably become refractory to chemotherapy, resulting in disease progression and death. The two major reasons for the poor prognosis of this disease are metastasis and chemoresistance.

Many of the signaling pathways activated in the cancer cells originate in the tumor microenvironment and play different roles during malignant transformation. Contrary to other solid tumors, the ovarian cancer microenvironment comprises the peritoneal cavity and the factors secreted by the different tissues and cells, including adipocyte cells, mesothelial cells, immune cells, and tissue fibroblasts, which will impact the response and behavior of malignant cells. This Special Issue will highlight the current state of the art in terms of the molecular signals originating from the tumor microenvironment that regulate malignant cells’ transformation, metastatic potential, and chemoresistance.

Scope: Molecular pathways responsible for mesenchymal transformation and chemoresistance.

Aims: This Special Issue aims to provide a platform for new findings related to the tumor microenvironment and the molecular pathways associated with ovarian cancer progression and chemoresistance. In this Special Issue, both original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Molecular signals originating from the tumor microenvironment responsible for the process of mesenchymal transformation;
  • The role of exosomes in the transformation of ovarian cancer cells;
  • The influence of the stroma on malignant progression;
  • Adipocytes and their role in malignant progression;
  • Metabolic adaptation and pathways conferring mesenchymal transformation;
  • The role of the signals initiated in the microenvironment responsible for chemoresistance;
  • Inflammatory signals and malignant progression.

Dr. Gil Mor
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • chemoresistance
  • epithelial mesenchymal transformation
  • metastasis
  • signaling pathways
  • immune modulation

Published Papers (3 papers)

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Research

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17 pages, 3539 KiB  
Article
A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype
by Radhika P. Gogoi, Sandra Galoforo, Alexandra Fox, Colton Morris, Harry Ramos, Vir K. Gogoi, Hussein Chehade, Nicholas K. Adzibolosu, Chenjun Shi, Jitao Zhang, Roslyn Tedja, Robert Morris, Ayesha B. Alvero and Gil Mor
Cancers 2023, 15(19), 4834; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15194834 - 02 Oct 2023
Viewed by 1073
Abstract
Background: Epithelial–mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation [...] Read more.
Background: Epithelial–mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation have been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify the genes responsible for maintaining the epithelial phenotype and inhibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expression was determined via qPCR and Western blot analysis. The knockout of CTGF was completed using the CTGF sgRNA CRISPR/CAS9. The tumorigenic potential was determined using NCG mice. Results: The knockout of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as anoikis resistance, cytoskeleton remodeling, increased cell stiffness, and the acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation. Full article
(This article belongs to the Special Issue Multiple Signaling Pathways in Ovarian Cancer)
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20 pages, 4642 KiB  
Article
Generation of Stable Epithelial–Mesenchymal Hybrid Cancer Cells with Tumorigenic Potential
by Roslyn Tedja, Ayesha B. Alvero, Alexandra Fox, Carlos Cardenas, Mary Pitruzzello, Hussein Chehade, Tejeshwhar Bawa, Nicholas Adzibolosu, Radhika Gogoi and Gil Mor
Cancers 2023, 15(3), 684; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030684 - 22 Jan 2023
Cited by 4 | Viewed by 1685
Abstract
Purpose: Cancer progression, invasiveness, and metastatic potential have been associated with the activation of the cellular development program known as epithelial-to-mesenchymal transition (EMT). This process is known to yield not only mesenchymal cells, but instead an array of cells with different degrees of [...] Read more.
Purpose: Cancer progression, invasiveness, and metastatic potential have been associated with the activation of the cellular development program known as epithelial-to-mesenchymal transition (EMT). This process is known to yield not only mesenchymal cells, but instead an array of cells with different degrees of epithelial and mesenchymal phenotypes with high plasticity, usually referred to as E/M hybrid cells. The characteristics of E/M hybrid cells, their importance in tumor progression, and the key regulators in the tumor microenvironment that support this phenotype are still poorly understood. Methods: In this study, we established an in vitro model of EMT and characterized the different stages of differentiation, allowing us to identify the main genomic signature associated with the E/M hybrid state. Results: We report that once the cells enter the E/M hybrid state, they acquire stable anoikis resistance, invasive capacity, and tumorigenic potential. We identified the hepatocyte growth factor (HGF)/c-MET pathway as a major driver that pushes cells in the E/M hybrid state. Conclusions: Herein, we provide a detailed characterization of the signaling pathway(s) promoting and the genes associated with the E/M hybrid state. Full article
(This article belongs to the Special Issue Multiple Signaling Pathways in Ovarian Cancer)
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Review

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16 pages, 329 KiB  
Review
Optimal First-Line Medico-Surgical Strategy in Ovarian Cancers: Are We There Yet?
by Stanislas Quesada, Quentin Dominique Thomas, Pierre-Emmanuel Colombo and Frederic Fiteni
Cancers 2023, 15(14), 3556; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15143556 - 10 Jul 2023
Cited by 3 | Viewed by 1319
Abstract
In spite of tremendous advances in advanced ovarian cancer management through the past decade, notably owing to surgical expertise and novel combination molecules (including bevacizumab and PARP inhibitors), the optimal initial sequential strategy remains a major concern. Indeed, following seminal clinical trials, primary [...] Read more.
In spite of tremendous advances in advanced ovarian cancer management through the past decade, notably owing to surgical expertise and novel combination molecules (including bevacizumab and PARP inhibitors), the optimal initial sequential strategy remains a major concern. Indeed, following seminal clinical trials, primary cytoreductive surgery (PCS) followed by adjuvant systemic therapy and interval cytoreductive surgery (ICS) following neoadjuvant chemotherapy (NACT) have been positioned as validated alternatives with distinct pros and cons, although a definite response is still unassessed. In clinical practice, decisions between PCS and ICS rely on multilayer parameters: the tumor itself, the patient, and the health structure. In this state-of-the-art review, we will discuss the current evidence based on clinical trials and real-world data and highlight the remaining questions, including the fittest positioning of PCS vs. ICS and the optimal number of NACT cycles; subsequently, we will discuss current axes of research such as dedicated clinical trials and more global perspectives. These ongoing strategies and perspectives could contribute to improving the patient journey through personalized medicine. Full article
(This article belongs to the Special Issue Multiple Signaling Pathways in Ovarian Cancer)
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