Autophagy: New Insights into Its Roles in Cancer Progression and Drug Resistance

Autophagy is a mechanism of lysosomal proteolysis that is utilized to degrade damaged organelles, proteins, and other cellular components. Although key studies demonstrate that autophagy functions as a mechanism of tumor suppression via the degradation of defective pre-malignant cells, autophagy can also be used as a mechanism to break down cellular components under stress conditions to generate the required metabolic materials for cell survival. Autophagy has emerged as an important mediator of resistance to radiation, chemotherapy, and targeted agents. This series of articles highlight the role of autophagy in cancer progression and drug resistance and underscores the need for new and more effective agents that target this process.

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The role of microvesicles in cancer progression and drug resistance

Biochemical Society Transactions ◽

10.1042/bst20120273 ◽

2013 ◽

Vol 41 (1) ◽

pp. 293-298 ◽

Cited By ~ 24

Author(s):

Samireh Jorfi ◽

Jameel M. Inal

Keyword(s):

Drug Resistance ◽

Multidrug Resistance ◽

Cancer Progression ◽

Chemotherapeutic Agents ◽

Malignant Cells ◽

Intercellular Transport ◽

Wide Range ◽

Anti Cancer ◽

Mdr Multidrug Resistance

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

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A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽

10.1182/blood-2014-03-557298 ◽

2014 ◽

Vol 124 (13) ◽

pp. 2061-2071 ◽

Cited By ~ 48

Author(s):

Zhiqiang Liu ◽

Jingda Xu ◽

Jin He ◽

Yuhuan Zheng ◽

Haiyan Li ◽

...

Keyword(s):

Drug Resistance ◽

Cell Survival ◽

Sonic Hedgehog ◽

Hedgehog Signaling ◽

Critical Role ◽

Myeloma Cell ◽

Sonic Hedgehog Signaling ◽

Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

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Role of Sigma-1 Receptor in Calcium Modulation: Possible Involvement in Cancer

Genes ◽

10.3390/genes12020139 ◽

2021 ◽

Vol 12 (2) ◽

pp. 139

Author(s):

Ilaria Pontisso ◽

Laurent Combettes

Keyword(s):

Cell Survival ◽

Cancer Progression ◽

Strong Impact ◽

Protective Function ◽

Sigma 1 Receptor ◽

Contact Sites ◽

Calcium Modulation ◽

Sigma 1 ◽

Cancer Cell Survival

Ca2+ signaling plays a pivotal role in the control of cellular homeostasis and aberrant regulation of Ca2+ fluxes have a strong impact on cellular functioning. As a consequence of this ubiquitous role, Ca2+ signaling dysregulation is involved in the pathophysiology of multiple diseases including cancer. Indeed, multiple studies have highlighted the role of Ca2+ fluxes in all the steps of cancer progression. In particular, the transfer of Ca2+ at the ER-mitochondrial contact sites, also known as mitochondrial associated membranes (MAMs), has been shown to be crucial for cancer cell survival. One of the proteins enriched at this site is the sigma-1 receptor (S1R), a protein that has been described as a Ca2+-sensitive chaperone that exerts a protective function in cells in various ways, including the modulation of Ca2+ signaling. Interestingly, S1R is overexpressed in many types of cancer even though the exact mechanisms by which it promotes cell survival are not fully elucidated. This review summarizes the findings describing the roles of S1R in the control of Ca2+ signaling and its involvement in cancer progression.

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Autophagy-Lysosomal Pathway as Potential Therapeutic Target in Parkinson’s Disease

Cells ◽

10.3390/cells10123547 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3547

Author(s):

Srinivasa Reddy Bonam ◽

Christine Tranchant ◽

Sylviane Muller

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Quality Control ◽

Cell Survival ◽

Control Systems ◽

Therapeutic Strategies ◽

Cell Type ◽

Potential Therapeutic Target ◽

Cellular Components

Cellular quality control systems have gained much attention in recent decades. Among these, autophagy is a natural self-preservation mechanism that continuously eliminates toxic cellular components and acts as an anti-ageing process. It is vital for cell survival and to preserve homeostasis. Several cell-type-dependent canonical or non-canonical autophagy pathways have been reported showing varying degrees of selectivity with regard to the substrates targeted. Here, we provide an updated review of the autophagy machinery and discuss the role of various forms of autophagy in neurodegenerative diseases, with a particular focus on Parkinson’s disease. We describe recent findings that have led to the proposal of therapeutic strategies targeting autophagy to alter the course of Parkinson’s disease progression.

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Hedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma

Oncotarget ◽

10.18632/oncotarget.8253 ◽

2016 ◽

Vol 7 (17) ◽

pp. 24179-24193 ◽

Cited By ~ 19

Author(s):

Erh-Hsuan Lin ◽

Yu-Rung Kao ◽

Chih-An Lin ◽

Ting-Yu Kuo ◽

Sheng-Ping Yang ◽

...

Keyword(s):

Drug Resistance ◽

Lung Adenocarcinoma ◽

Cell Survival ◽

Stress Conditions ◽

Hedgehog Pathway

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The Role of Caveolin‐1 in Tumor Cell Survival and Cancer Progression

Lipid Rafts and Caveolae ◽

10.1002/3527608079.ch12 ◽

2006 ◽

pp. 249-263

Author(s):

Dana Ravid ◽

Mordechai Liscovitch

Keyword(s):

Tumor Cell ◽

Cell Survival ◽

Cancer Progression ◽

Caveolin 1 ◽

Tumor Cell Survival

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Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

The International Journal of Biological Markers ◽

10.1177/1724600820906155 ◽

2020 ◽

Vol 35 (1_suppl) ◽

pp. 8-11 ◽

Cited By ~ 3

Author(s):

Paola Nisticò ◽

Gennaro Ciliberto

Keyword(s):

Tumor Microenvironment ◽

Tumor Cells ◽

Cancer Progression ◽

Cancer Biology ◽

Tumor Development ◽

Short Paper ◽

Great Relevance ◽

Cellular Components ◽

The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

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Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Cancers ◽

10.3390/cancers12020396 ◽

2020 ◽

Vol 12 (2) ◽

pp. 396

Author(s):

Estíbaliz Tamayo-Orbegozo ◽

Laura Amo ◽

Javier Díez-García ◽

Elena Amutio ◽

Marta Riñón ◽

...

Keyword(s):

Drug Resistance ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cancer Progression ◽

Current Knowledge ◽

Cell Types ◽

Metabolic Reprogramming ◽

Non Hodgkin Lymphoma ◽

New Evidence

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

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