Lecture 10: Cancer and Development

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Questions and Answers

What is the consequence of mutations in APC genes in stem cells?

Formation of large polyps that progress to cancer (correct)

Formation of small, non-progressive tumors

Immediate activation of the immune response

Complete resistance to all tumor formation

Which mechanism is associated with self-sufficiency in growth signals in cancer cells?

Inactivation of the RB gene

Overexpression of E-cadherin

Inhibition of telomerase activity

Activation of the Ras oncogene (correct)

How does the loss of function in retinoblastoma (RB) or APC genes affect cell cycle progression?

It results in enhanced negative regulation of the cell cycle.

It prevents any mutations from occurring in the cells.

It allows for unregulated cell cycle progression. (correct)

It induces premature cell death.

What role does E-cadherin play in epithelial tissues?

Maintains cell-cell adhesion (D) Signup and view all the answers

What is the significance of the activation of SNE1 in cancer progression?

It contributes to epithelial-to-mesenchymal transition (EMT). (D) Signup and view all the answers

What is the effect of telomerase activation on cancer cells?

It allows for indefinite cell division. (A) Signup and view all the answers

What characterizes the tumors formed by mutations in APC in transit amplifying cells?

They are small and non-progressive. (C) Signup and view all the answers

Which of the following statements best describes a hallmark of cancer related to uncontrolled growth?

Cancer cells possess self-sufficiency in growth signals. (C) Signup and view all the answers

What role does APC play in the regulation of the cell cycle?

It negatively regulates cell cycle progression. (B) Signup and view all the answers

Which mutation is primarily associated with Gorlin Syndrome?

Inactivating mutations of Patched 1 (B) Signup and view all the answers

What is the most significant effect of cyclopamine on the Hedgehog signaling pathway?

Inhibition of Smoothened movement to the primary cilium (D) Signup and view all the answers

Which of the following cancers is NOT directly associated with the Hedgehog/Patched signaling pathway?

Hepatocellular carcinoma (B) Signup and view all the answers

What congenital abnormality was identified in the cyclopic lambs related to cyclopamine?

Severe brain defects (D) Signup and view all the answers

Which of the following is a consequence of GLI1 amplification in cancer?

All of the above (D) Signup and view all the answers

In which type of cancer are activating mutations of Smoothened commonly involved?

Basal Cell Carcinoma (A) Signup and view all the answers

What is the initial consequence of mutations in both alleles of the APC tumor suppressor gene in stem cells?

Development of aberrant crypts and early adenomas (A) Signup and view all the answers

Which mutation drives the development of larger adenomas as cancer progresses?

Activation of the KRAS oncogene (B) Signup and view all the answers

What role does the microenvironment play in cancer progression, according to the branch model?

It influences the trajectory of development and mutation accumulation (D) Signup and view all the answers

What happens when both alleles of the p53 gene are mutated during cancer progression?

There is loss of function, promoting cancer progression (A) Signup and view all the answers

Which of the following is NOT a characteristic of tumor heterogeneity?

Tumors develop from a strictly linear process (B) Signup and view all the answers

What is the role of epithelial-to-mesenchymal transition (EMT) genes in cancer progression?

Inactivating abilities to invade other organs (B) Signup and view all the answers

What is primarily affected by mutations in the oncogene beta-catenin?

Cell growth regulation leading to hyperproliferation (B) Signup and view all the answers

Which factor is NOT described as influencing the accumulation of distinct mutations in cancer cells?

The genetic stability of the tumor suppressor genes (A) Signup and view all the answers

In cancer development, what is the significance of stem cells accumulating mutations?

They likely lead to tumor heterogeneity within the cancer (A) Signup and view all the answers

What contributes to excessive proliferation in the early stages of adenoma formation?

Accumulation of mutations in stem cells (C) Signup and view all the answers

What is the primary role of vascular endothelial growth factor (VEGF) in tumor biology?

It facilitates the formation of new blood vessels. (C) Signup and view all the answers

Which factor is commonly utilized by cancer cells to evade apoptosis?

Insulin-like Growth Factor (IGF) (D) Signup and view all the answers

What role do oncogenes like KRAS play in normal cells?

They activate the cell cycle and promote cell proliferation. (C) Signup and view all the answers

What is the outcome of a mutation in a single copy of an oncogene?

It leads to a dominant effect promoting abnormal cell behavior. (A) Signup and view all the answers

Which of the following best describes the function of tumor suppressor genes in normal cells?

They inhibit cell division. (D) Signup and view all the answers

What triggers the activation of telomerase in the context of cancer development?

A mutation in oncogenes. (B) Signup and view all the answers

Which mutation sequence is common in the progression of cancer development?

Loss of APC followed by KRAS mutation. (C) Signup and view all the answers

How can mutations in APC affect cancer progression?

By facilitating insensitivity to anti-growth signals. (C) Signup and view all the answers

What is a hallmark characteristic of oncogenes when they are mutated?

They show overproduction or hyperactivation. (D) Signup and view all the answers

What defines the sequence of mutations leading to cancer formation?

Different tumor types can acquire mutations in varying sequences. (D) Signup and view all the answers

What happens to beta-catenin when the Wnt pathway is inactive?

Beta-catenin is degraded by the proteasome (C) Signup and view all the answers

Which of the following is a result of Wnt ligand binding to the Frizzled receptor?

Dissociation of the destruction complex (D) Signup and view all the answers

Familial Tooth Agenesis Syndrome is associated with which specific mutation?

Loss of both copies of the AXIN2 allele (C) Signup and view all the answers

What is the role of AXIN2 in the Wnt signaling pathway?

Forms part of the destruction complex (A) Signup and view all the answers

What phenotype is prominently observed in male patients with Familial Tooth Agenesis Syndrome?

Oligodontia (A) Signup and view all the answers

How does aberrant regulation of Wnt signaling potentially affect cancer formation?

By inducing abnormal stem cell proliferation (C) Signup and view all the answers

What is the consequence of a disrupted negative feedback loop in Wnt signaling?

Decreased activity of the destruction complex (B) Signup and view all the answers

Which of the following Wnt target genes is activated when Wnt signaling is properly initiated?

MYC (C) Signup and view all the answers

What role does the Wnt signaling pathway play in tooth formation?

It is essential for maintaining dental stem cells (A) Signup and view all the answers

What is the initial step in the activation of the Wnt signaling pathway?

Binding of Wnt ligand to the Frizzled receptor (A) Signup and view all the answers

Study Notes

Cancer Development and Mutations

Mutations in the APC gene in transit amplifying cells result in small, non-progressive tumors, while mutations in stem cells lead to large polyps that can progress to cancer.
Key conclusion: Colon cancer originates from stem cells.

Hallmarks of Cancer

Self-sufficiency in growth signals: Activation of the Ras oncogene causes uncontrolled cell proliferation.
Insensitivity to anti-growth signals: Loss of function in tumor suppressor genes like retinoblastoma (RB) or APC removes regulation of the cell cycle.
Tissue invasion and metastasis: Inactivation of E-cadherin allows cells to invade surrounding tissues, and activation of SNE1 facilitates epithelial-to-mesenchymal transition (EMT).
Limitless replicative potential: Activation of telomerase enables cancer cells to divide indefinitely by maintaining telomere integrity.
Sustained angiogenesis: Production of vascular endothelial growth factor (VEGF) supports tumor growth by promoting blood vessel formation.
Evasion of apoptosis: Cancer cells evade programmed cell death through factors like Insulin-like Growth Factor (IGF).

Tumor Progression

Cancer progression involves the accumulation of mutations, such as APC mutation followed by KRAS mutation, leading to larger adenomas and eventual cancer.
Loss of p53 function drives the transition from adenoma to cancer, allowing cells to invade other organs.

Tumor Heterogeneity

Tumors consist of diverse cell types, indicating a non-linear progression influenced by the microenvironment and interactions with other cell populations.

Wnt Signaling Pathway

In the inactive state, the destruction complex phosphorylates β-catenin for degradation, preventing Wnt target gene activation.
Active pathway involves Wnt ligand binding to Frizzled, resulting in β-catenin accumulation and activation of genes like MYC and AXIN2.
Proper regulation of Wnt signaling is crucial; disruption can lead to severe phenotypes, such as oligodontia in Familial Tooth Agenesis Syndrome due to AXIN2 mutations.

Sonic Hedgehog Signaling Pathway

Hedgehog signaling is critical during developmental processes; mutations are linked to various tumors.
Inactivating mutations of Patched 1 are associated with Gorlin Syndrome and basal cell carcinoma.
Activating mutations of Smoothened lead to pathway activation implicated in basal cell carcinoma and medulloblastoma.

Cyclopamine Discovery

Cyclopic lambs born from ewes consuming corn lily had severe deformities; studies identified cyclopamine as a compound affecting Hedgehog signaling.
Cyclopamine inhibits Hedgehog signaling by binding to Smoothened, blocking its migration to the primary cilium, thus holding potential for anti-cancer therapy.

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Description

This quiz covers key concepts related to cancer and its development, specifically focusing on mutations in APC and their impact on tumor progression. It highlights the role of stem cells in colon cancer and the implications for understanding this disease. Test your knowledge on the factors influencing cancer development.