Cell Biology: Epithelial Cells, Stem Cells, and Cancer

What type of cells line ducts, lumens, and tubes?

Epithelial cells.

What is the role of the extracellular matrix (ECM) in tissues?

It defines the boundary between tissue types and provides structural support.

Name the three types of epithelial cells shown in the chapter.

Columnar, squamous, and cuboidal.

What is the basal lamina?

A specialized layer of ECM that underlies epithelial cells and separates them from connective

tissue.

What happens when a stem cell divides?

Each daughter cell can either remain a stem cell (self-renewal) or differentiate into a specialized cell.

What is required for differentiation vs. stem cell fate decisions?

Specific changes in gene transcription are required.

Why do differentiated cells no longer divide?

They shut down the cell cycle control system.

Where are intestinal stem cells located?

Located at the bottom of intestinal crypts within the connective tissue.

What are transit-amplifying cells?

Dividing precursor cells generated by intestinal stem cells that divide 3-4 times before differentiating.

What are the two main types of cells produced by intestinal stem cells?

Absorptive brush-border cells and mucus-secreting goblet cells.

How long does it take for epithelial cells to migrate from the crypt to the villus tip in humans?

It takes 3-6 days for epithelial cells to migrate from the crypt to the villus tip in humans.

What happens to cells at the top of the villus?

They differentiate, die, and slough off into the gut lumen.

What signaling pathway maintains stem cell fate in the gut?

Wnt signaling pathway

What happens when the Wnt pathway is active?

β-catenin is stabilized, leading to transcription of Wnt-responsive genes and proliferation of gut stem cells.

What is the role of APC in the Wnt pathway?

APC promotes the degradation of β-catenin when the Wnt pathway is inactive.

What type of epithelium is the epidermis?

A stratified epithelium renewed from stem cells in its basal layer.

What happens to cells in the epidermis as they move outward?

They die, flatten, and become packed with keratin filaments, eventually shedding as scales.

What is the origin of all blood cells?

Hematopoietic stem cells.

What does it mean for stem cells to be multipotent?

They can differentiate into multiple cell types within a specific lineage (e.g., blood cells).

What is the key difference between embryonic stem cells and adult stem cells?

Embryonic stem cells are pluripotent (can form all cell types in the organism), while adult stem cells are multipotent or unipotent.

How are embryonic stem cells maintained in culture?

They are grown in the presence of leukemia inhibitory factor (LIF) to prevent differentiation.

What are iPS cells, and how are they created?

Induced pluripotent stem cells; adult cells are de-differentiated using transcription factors like Oct4, Sox2, and Klf4.

What is a therapeutic use for iPS cells?

They can be used to study disease mechanisms, screen drugs, or generate healthy cells for transplantation.

How are organoids produced?

By triggering stem cells to differentiate into specific tissue types using transcription factors and growth factors.

What defines a cancerous cell as malignant?

It invades surrounding tissues and can metastasize to form secondary tumors.

What is the most common type of epithelial cancer?

Carcinoma.

What is metastasis?

The spread of cancer cells to new locations to establish secondary tumors.

Why do cancer rates increase with age?

Accumulation of mutations over time in genes involved in DNA repair, cell cycle control, etc.

What are four cellular activities whose mutations can increase cancer risk?

DNA replication, DNA repair, cell-cycle checkpoint signaling, and apoptosis signaling.

DNA replication

The process by which a cell duplicates its DNA before cell division.

DNA repair

The mechanisms by which a cell identifies and corrects damage to its DNA.

cell-cycle checkpoint signaling

Regulatory pathways that ensure the proper progression of the cell cycle.

apoptosis signaling

The process that leads to programmed cell death in response to cellular stress or damage.

What is a hallmark of advanced tumors?

Highly abnormal chromosomes due to genetic instability.

What is a proto-oncogene?

A normal gene that promotes cell division/survival; mutations can make it overactive (oncogenic).

What is a tumor suppressor gene?

A gene that prevents cell division or promotes apoptosis; mutations inactivate it.

How do mutations in proto-oncogenes and tumor suppressor genes differ in dominance?

Proto-oncogene mutations are dominant (gain-of-function), while tumor suppressor mutations are recessive (loss-of-function).

Name three ways proto-oncogenes can be activated.

Mutation in coding sequence, gene amplification, or chromosome rearrangement.

Name three ways tumor suppressor genes can be inactivated.

Loss-of-function mutation, chromosome deletion, or epigenetic silencing.

What is the role of APC in colon cancer?

Loss of both APC copies leads to excessive proliferation of intestinal crypt cells.

What are examples of cancer-critical genes?

Ras (proto-oncogene), β-catenin (proto-oncogene), p53 (tumor suppressor), APC (tumor suppressor).

How does p53 protect against cancer?

It halts the cell cycle or triggers apoptosis in response to DNA damage.

What is a new treatment targeting immune checkpoints?

Anti-immune-checkpoint antibodies that allow killer cells to attack tumors.

How can tumors be targeted with antibodies?

Some tumors produce unique proteins not found in normal cells, allowing antibody specificity.

What is the sequence of mutations leading to invasive colon cancer?

APC loss → Ras activation → additional tumor suppressor losses (e.g., p53) → metastasis.

What is the difference between a benign polyp and invasive cancer?

A polyp is localized; invasive cancer breaks through the basal lamina and spreads.

What are Brca1 and Brca2, and how do they relate to cancer?

Tumor suppressor genes; their inactivation allows survival despite DNA damage (e.g., breast

cancer).

What are the four phases of the cell cycle?

G1, S, G2, and M phases.

What happens during the G1 phase?

Protein synthesis, growth, and decision-making about cell division.

What is the key event of the S phase?

DNA synthesis (replication).

What prepares during the G2 phase?

Protein synthesis and growth for mitosis.

What are the two main events of M phase?

Mitosis (nuclear division) and cytokinesis (cytoplasmic division).

What regulates progression through the cell cycle?

The cell-cycle control system, involving cyclin-dependent kinases (Cdks) and checkpoints.

What are the three major checkpoints in the cell cycle?

G1 checkpoint, G2 checkpoint, and metaphase checkpoint.

What question does the G1 checkpoint answer?

"Is the environment favorable for division?"

What is the role of cyclin-dependent kinases (Cdks)?

They phosphorylate target proteins to drive cell cycle events when bound to cyclins.

How are Cdks activated?

By binding to cyclins and phosphorylation by CAK (activating) or Wee1 (inhibitory).

What removes the inhibitory phosphate on Cdks?

The phosphatase Cdc25.

What happens if DNA damage is detected at the G1 checkpoint?

p53 triggers p21 production, which inhibits Cdks to halt the cycle.

What is the "START" checkpoint in yeast?

The point in G1 where the cell commits to division.

How does Rb protein regulate the G1 checkpoint?

It represses transcription factors until phosphorylated by G1/S-Cdks, releasing them to

activate S-phase genes.

What triggers DNA replication in S phase?

S-Cdk phosphorylates Cdc6 (degradation), ORC (inactivation), and helicases (activation).

S-Cdk

Phosphorylates Cdc6 (degradation), ORC (inactivation), and helicases (activation) to trigger DNA replication in S phase.

What is the role of M-Cdk in mitosis?

Triggers chromosome condensation, nuclear envelope breakdown, Golgi fragmentation, and spindle formation during mitosis.

What is another name for M-Cdk?

Maturation promoting factor (MPF)

How is M-Cdk inactivated?

APC/C ubiquitinates its cyclin, targeting it for proteasomal degradation.

What does APC/C do during anaphase?

Ubiquitinates securin, freeing separase to cleave cohesins and separates chromatids.

What happens if chromosomes are not properly attached to the spindle?

The metaphase checkpoint delays anaphase until attachments are correct.

What phosphorylates nuclear lamins and pore proteins during mitosis?

M-Cdk.

What is the difference between apoptosis and necrosis?

Apoptosis is programmed, energy-dependent cell death; necrosis is uncontrolled cell death

due to injury.

What is necrosis?

Uncontrolled cell death due to injury.

What are caspases, and what do they do?

Proteases that execute apoptosis by cleaving targets like lamins, cytoskeletal proteins, and DNase inhibitors.

How are caspases activated?

Initiator caspases dimerize and cleave effector caspases, amplifying the apoptotic signal.

What is the role of cytochrome c in apoptosis?

Activates the apoptosome, which recruits and activates caspase-9 in apoptosis.

How does Bcl-2 inhibit apoptosis?

Inhibits apoptosis by blocking Bax/Bak, preventing mitochondrial pore formation and cytochrome c release.

What is myostatin, and what happens if it is mutated?

A signal that inhibits muscle growth; mutations lead to excessive muscle growth.

What ensures proper neuron-target cell matching during development?

Apoptosis of neurons that do not receive enough survival factors from target cells.

What is the role of p53 in the cell cycle?

Halts the cell cycle or triggers apoptosis in response to DNA damage.

What happens if p53 is inactive?

Results in cells with damaged DNA continuing to divide, increasing cancer risk.

What proteins are targeted by M-Cdk during mitosis?

Condensins, lamins, nuclear pore proteins, Golgi matrix proteins, and centrosome proteins.

What proteins are targeted by S-Cdk during DNA replication?

Cdc6, ORC, and helicases.

How is M-Cdk positively regulated?

By binding to cyclin and phosphorylation by CAK.

How is M-Cdk negatively regulated?

By inhibitory phosphorylation (Wee1) and inhibitor proteins (e.g., p27).

What is the role of the anaphase-promoting complex (APC/C)?

It ubiquitinates securin and cyclins to promote anaphase and exit from mitosis.

What happens if DNA replication is incomplete at the G2 checkpoint?

The cycle is halted until replication is finished.

What is the role of cohesins in mitosis?

Hold sister chromatids together until anaphase.

What triggers the fragmentation of the nucleus during apoptosis?

caspase-mediated cleavage of lamins.

How do phagocytic cells recognize apoptotic cells?

By phosphatidylserine exposed on the outer membrane.

What is the role of p21 in the cell cycle?

Inhibits Cdks to halt the cycle in response to DNA damage.

What is the consequence of chromosome missegregation?

Aneuploidy (abnormal chromosome numbers), which can lead to cancer.

How does the cell ensure proper sequence of cell cycle events?

checkpoints and dependencies (e.g., S-Cdk activates M-Cdk).

What is the role of Cdc6 in DNA replication?

It helps load helicases onto origins; S-Cdk phosphorylates it for degradation.

What happens if the nuclear envelope fails to break down during mitosis?

Chromosomes cannot properly attach to the spindle, leading to segregation errors.

How do survival factors inhibit apoptosis?

They activate transcription of anti-apoptotic genes like Bcl-2.