Ciliated, Mitochondria-Rich Postmitotic Cells are Immune-privileged, and Mimic Immunosuppressive Microenvironment of Tumor-Initiating Stem Cells: From Molecular Anatomy to Molecular Pathway

Abstract

Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading cause of death worldwide. Tumorinitiating stem cells (TiSCs) are a subset of the tumor population responsible for tumor resistance and relapse. Understanding the characteristics and shared features between tumor-initiating stem cells (TiSCs) and long-lived postmitotic cells may hold a key to better understanding the biology of cancer. Postmitotic cells have exited the cell cycle and are transitioned into a non-dividing and terminally differentiated state with a specialized function within a tissue. Conversely, a cancer cell with TiSC feature can divide and produce a variety of progenies, and is responsible for disease progression, tumor resistance to therapy and immune system and disease relapse. Surprisingly, our comprehensive evaluation of TiSCs suggests common features with long-lived post-mitotic cells. They are similar in structure (primary cilia, high mitochondrial content, and being protected by a barrier), metabolism (autophagy and senescence), and function (immunoescape and/or immune-privileged by a blood barrier). In-depth exploration showed how mitochondrial metabolism contributes to these shared features, including high energy demands arising from ciliary and microtubular functionality, increased metabolic activity, and movement. These findings can assist in decoding the remaining properties which offer insights into the biology of TiSCs, with potential implications for enhancing cancer treatment strategies and patient prognosis.

Overcoming Chemotherapy Resistance in Metastatic Cancer: A Comprehensive Review

“…CSCs are a subgroup of tumor cells that cause tumor resistance and recurrence. A cancer cell with the stem cell characteristic (including its similarities with long-lived postmitotic cells) may divide and create a wide range of progenies; it is responsible for disease progression, tumor resistance to therapy and the immune system, and disease recurrence [152].…”

Polyploidy Promotes Hypertranscription, Apoptosis Resistance, and Ciliogenesis in Cancer Cells and Mesenchymal Stem Cells of Various Origins: Comparative Transcriptome In Silico Study

“…Ciliogenesis also protects cells from apoptosis. Thus, primary cilia stabilization may reduce the abortive cell cycle re-entry to protect injured postmitotic neurons from apoptosis [120,121]. Additionally, ciliogenesis protects cells from immunosurveillance thereby enabling them to immunoescape [121].…”

“…Thus, primary cilia stabilization may reduce the abortive cell cycle re-entry to protect injured postmitotic neurons from apoptosis [120,121]. Additionally, ciliogenesis protects cells from immunosurveillance thereby enabling them to immunoescape [121]. The overactivation of primary cilia can increase the anticancer drug resistance [122].…”