Cancer stem cells & Oncogenes pt. 1 Lecture 2

What are the defining characteristics of a cancer stem cell (CSC)?

It is a small subpopulation of tumor cells that can self-renew and differentiate into other types of cancer cells, thereby driving tumor initiation and growth.

How do CSCs differ from normal adult stem cells?

Normal adult stem cells are multipotent, meaning they can only produce a limited set of differentiated cell types within a tissue. CSCs have the potential to generate an entire heterogeneous tumor.

What are the two possible origins of a CSC?

it can arise from the transformation of a normal stem cell through mutations or from the dedifferentiation of a committed progenitor or differentiated cell that regains the ability to self

Why are CSCs thought to be responsible for tumor recurrence?

Traditional chemotherapy targets fast-growing cells, but CSCs are often relatively quiescent and can be resistant to many drugs. This can allow them to survive treatment and regenerate the tumor.

What are some resistance mechanisms of CSCs to chemotherapy?

can express drug-efflux pumps and other proteins that actively remove chemotherapy drugs from the cell. They can also exist in a quiescent, non-dividing state which makes them less susceptible to drugs that target cell division.

What are the two modes of asymmetric division for a cancer stem cell?

The outcome can be predetermined by the intrinsic nature of the stem cell, or it can be determined by the niche signals and space (neutral competition).

What is the difference between an oncogene and a proto-oncogene?

A proto-oncogene is a normal gene that has the potential to become an oncogene. An oncogene is an abnormally expressed or mutated form of a proto-oncogene that has the potential to cause cancer.

How can a proto-oncogene be converted into an oncogene?

A proto-oncogene can become an oncogene through point mutation, gene amplification, or chromosomal rearrangement, leading to an overactive or overexpressed protein.

What are the functions of the protein products of proto-oncogenes?

They are typically involved in regulating normal cellular processes, such as cell proliferation, differentiation, and survival.

What is the significance of the Src oncogene?

Src was the first identified oncogene, discovered in a chicken virus (Rous Sarcoma Virus or RSV). The discovery of its normal cellular counterpart, c-Src, confirmed that oncogenes are derived from normal cellular genes.

How does the Ras proto-oncogene become an oncogene?

It is a G-protein that cycles between an inactive (GDP-bound) state and an active (GTP-bound) state. It becomes an oncogene primarily through a point mutation (e.g., G12V) that causes it to lose its GTPase activity, trapping it in the active state and leading to continuous signaling.

What are some of the other components of the Ras signaling pathway that can lead to cancer if mutated?

Mutations in components upstream of Ras, such as receptor tyrosine kinases (RTKs) like Her2, or in proteins that regulate Ras, such as GTPase-activating proteins (GAPs), can cause a gain-of-function activation of the pathway.