Lung Cancer Stem Cells, p53 Mutations and MDM2

Abstract

Over the past few decades, advances in cancer research have enabled us to understand the different mechanisms that contribute to the aberrant proliferation of normal cells into abnormal cells that result in tumors. In the pursuit to find cures, researchers have primarily focused on various molecular level changes that are unique to cancerous cells. In humans, about 50 % or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Despite the identification of numerous triggers that causes lung cancer specific cure still remain elusive. One of the primary reasons attributed to this is due to the fact that the tumor tissue is heterogeneous and contains numerous sub-populations of cells. Studies have shown that a specific sub-population of cells termed as cancer stem cells (CSCs) drive the recurrence of cancer in response to standard chemotherapy. These CSCs are mutated cells with core properties similar to those of adult stem cells. They reside in a microenvironment within the tumor tissue that supports their growth and make them less susceptible to drug treatment. These cells possess properties of symmetric self-renewal and migration thus driving tumor formation and metastasis. Therefore, research specifically targeting these cells has gained prominence towards developing new therapeutic agents against cancer. This chapter focuses on lung cancer stem cells, p53 mutations noted in these cells, and importance of MDM2 interactions. Further, research approaches for better understanding of molecular mechanisms that drive CSC function and developing appropriate therapies are discussed.

Activation of insulin-like growth factor 1 receptor regulates the radiation-induced lung cancer cell apoptosis

“…Cumulative reports demonstrate aberrant p53 expression in lung cancer (Gadepalli et al, 2014). We wondered if the triple complex of Fig.…”

Essential Oils of Lemongrass (Cymbopogon citratus Stapf) Induces Apoptosis and Cell Cycle Arrest in A549 Lung Cancer Cells

“…In Vietnam, 22,000 people are diagnosed with lung cancer and 19,500 die from the disease yearly. Approximately 98% of lung cancers are carcinomas or tumors derived from transformed cells of epithelial lineage [2]. Recently, nearly four dozen different histopathological variants of lung carcinoma have been recognized.…”

A novel function of AAA-ATPase p97/VCP in the regulation of cell motility

“…Most cancer deaths are a result of the development of metastatic properties in tumors [23]. Understanding the mechanism that drives the uncontrolled migration of cancer cells is necessary for the prospect of an effective treatment against deadly cancers [24]. The process of metastasis is driven, in large part, by abnormal alterations in the cell migration properties of cells.…”