Growth Factors and Receptors in Cancer

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Questions and Answers

What is the primary role of p53 as a tumor suppressor protein?

Inducing apoptosis in all cells

Activating cyclin B1/Cdk1 for cell cycle progression

Regulating the expression of pro-apoptotic genes

Preventing cancer development by repairing DNA or inducing apoptosis (correct)

Which process is primarily regulated by p53 in response to cellular stress?

Cellular division

Protein synthesis

Metabolism

Apoptosis (correct)

Which protein does 14-3-3σ sequester in the cytoplasm to prevent mitotic activation?

GADD45

BAX

p53

Cyclin B1/Cdk1 (correct)

What happens when p53 detects severe DNA damage that cannot be repaired?

It activates the apoptotic machinery Signup and view all the answers

Which gene is known for promoting DNA repair processes regulated by p53?

GADD45 Signup and view all the answers

What is the function of BAX in the apoptotic pathway activated by p53?

To promote mitochondrial membrane permeabilization Signup and view all the answers

What percentage of human cancers involve mutations in the TP53 gene?

Approximately 50% Signup and view all the answers

How does p53 activate apoptosis transcriptionally?

By binding to specific DNA sequences to regulate gene expression Signup and view all the answers

What is the primary initiator caspase in the extrinsic apoptosis pathway?

Caspase-8 Signup and view all the answers

Which of the following processes occurs during the execution phase of apoptosis?

Cleavage of Nuclear Lamins Signup and view all the answers

What is the primary function of growth factor receptors?

To bind to specific growth factors and regulate cell processes Signup and view all the answers

Which proteins are considered pro-apoptotic regulators in the regulation of apoptosis?

Bax, Bak Signup and view all the answers

What is the outcome when caspase-8 cleaves Bid in the extrinsic pathway?

Promotion of mitochondrial outer membrane permeabilization (MOMP) Signup and view all the answers

Which type of growth factor receptor is most commonly associated with tyrosine kinase activity?

Tyrosine Kinase receptors Signup and view all the answers

Which cellular event is a hallmark of apoptosis?

DNA fragmentation Signup and view all the answers

What happens during the dimerization step of growth factor receptor activation?

Two receptor molecules pair together, activating the receptor Signup and view all the answers

In many cancers, dysregulation of which gene can prevent apoptosis and support tumor survival?

p53 Signup and view all the answers

What is the primary consequence of mutations in growth factor receptor pathways?

Uncontrolled signaling leading to cancer development Signup and view all the answers

What is a common receptor implicated in non-small cell lung cancer and colorectal cancer?

Epidermal growth factor receptor (EGFR) Signup and view all the answers

What is the role of IAPs (Inhibitors of Apoptosis Proteins) in apoptosis regulation?

Inhibit caspases Signup and view all the answers

Which downstream signaling pathway is NOT typically triggered by activated growth factor receptors?

Apoptotic pathway Signup and view all the answers

What is the result of macrophages or neighboring cells phagocytosing apoptotic bodies?

Prevention of inflammation Signup and view all the answers

What mechanism is primarily involved in terminating the signaling of growth factor receptors?

Receptor internalization or deactivation by regulatory proteins Signup and view all the answers

What therapeutic strategy is used for cancers with EGFR mutations?

EGFR inhibitors such as gefitinib and erlotinib Signup and view all the answers

What leads to uncontrolled receptor activation in non-small cell lung cancer (NSCLC)?

Mutations in the EGFR gene Signup and view all the answers

Which protein is initially activated by RAS-GTP in the MAPK/ERK pathway?

RAF Signup and view all the answers

How do mutations in KRAS affect the MAPK/ERK pathway?

They keep RAS in its active GTP-bound state Signup and view all the answers

What mutation is associated with continuous activation of the RAF kinase in cancer?

BRAF V600E mutation Signup and view all the answers

What is the role of PI3K in the PI3K/AKT pathway?

To phosphorylate PIP2 to form PIP3 Signup and view all the answers

Which mutation leads to increased AKT signaling in cancer?

PIK3CA mutation Signup and view all the answers

What is a function of the mTOR protein in the PI3K/AKT pathway?

Promoting protein synthesis and cell growth Signup and view all the answers

What is the effect of PTEN loss on the PI3K/AKT pathway?

Increases AKT signaling Signup and view all the answers

What role does autophagy play in the metastasis of cancer cells?

It promotes survival during detachment and colonization in distant organs. Signup and view all the answers

What is the significance of epithelial-to-mesenchymal transition (EMT) in cancer?

It allows cancer cells to acquire invasive and metastatic capabilities. Signup and view all the answers

How does autophagy assist cancer cells under hypoxic conditions?

By supporting adaptation to low-oxygen environments. Signup and view all the answers

What is a recent research focus regarding autophagy and cancer therapies?

Investigating autophagy inhibitors to reduce drug resistance. Signup and view all the answers

In what way does autophagy act as a double-edged sword in tumor progression?

It prevents initiation but later aids in tumor survival and aggressiveness. Signup and view all the answers

What mechanism do aggressive tumors often utilize to survive therapy due to increased autophagy?

They activate pathways leading to drug resistance. Signup and view all the answers

What is the primary effect of hypoxia on autophagy in cancer cells?

Hypoxia increases autophagy to help with survival. Signup and view all the answers

What therapeutic strategy is being explored to combat drug resistance in aggressive cancers?

Inhibiting autophagy in conjunction with chemotherapy. Signup and view all the answers

Study Notes

Growth Factors and Cancer

Growth factor receptors are surface proteins binding specific signaling molecules essential for growth, differentiation, and survival.

Types of Growth Factor Receptors

Tyrosine Kinase Receptors: Most prevalent; include EGFR, PDGF, and VEGFR.
G-Protein-Coupled Receptors (GPCRs): Bind various ligands and are implicated in cancer progression.
Serine/Threonine Receptors: Function through phosphorylation of serine or threonine residues affecting cellular signaling.

Mechanism of Growth Factor Receptors

Binding of growth factors induces receptor dimerization, activating intracellular domains.
Autophosphorylation occurs on specific tyrosine residues, launching downstream signaling pathways.
Key pathways activated include MAPK/ERK, PI3K/AKT, and JAK/STAT, influencing proliferation and survival.
Signaling termination happens via receptor internalization or regulatory protein deactivation, with mutations potentially leading to cancer.

Key Growth Factor Receptors in Cancer

Epidermal Growth Factor Receptor (EGFR):
- Normal Role: Regulates cell growth and differentiation.
- Cancer Role: Mutations and overexpression linked to lung and colorectal cancers, leading to uncontrolled proliferation.
- Targeted Therapy: EGFR inhibitors like gefitinib and erlotinib are used against EGFR mutations.

Extrinsic Pathway of Apoptosis

Begins with external death signals binding to death receptors.
Forms the death-inducing signaling complex (DISC) which activates caspase-8, initiating apoptosis.
Cross-talk with the intrinsic pathway promotes mitochondrial membrane permeabilization, leading to cell death.

Apoptosis Overview

Cancer cells can undergo both apoptosis and necrosis; apoptosis is a regulated process, frequently disrupted in cancers.
Many cancers exhibit dysregulation of apoptotic pathways, often linked to mutations in the p53 gene.
Cancer therapies aim to enhance apoptosis by targeting inhibitors like Bcl-2.

Pathways Involved in Cancer

MAPK/ERK Pathway:
- Key for regulating cell growth and differentiation.
- Activation involves RAS and RAF proteins leading to increased cell proliferation.
- Dysregulation through KRAS or BRAF mutations commonly seen in cancers like pancreatic and melanoma.
PI3K/AKT Pathway:
- Critical for cell survival and metabolism.
- Activation occurs through growth factor-induced PI3K activity, leading to AKT activation.
- PIK3CA mutations and PTEN loss promote increased signaling, enhancing survival and growth.

Role of p53 in Cancer

Known as the "guardian of the genome," p53 serves to prevent cancer progression by regulating the cell cycle and promoting apoptosis.
Over 50% of human cancers harbor mutations in the TP53 gene, undermining its tumor-suppressive function.
p53 can induce apoptosis through both transcriptional activation of pro-apoptotic genes and direct mechanisms.

Autophagy's Dual Role

Autophagy can enhance metastasis by allowing cancer cells to survive adverse conditions during circulation and colonization.
In hypoxic conditions, autophagy helps cells adapt by recycling damaged components, promoting survival under stress.
Autophagy can create resistance against cancer therapies, and inhibitors are being tested to leverage this in treatment strategies.

Summary of Findings

Autophagy's role shifts from a tumor suppressor in early stages to a promoter of growth and resistance in advanced tumors.
Targeting the mechanisms of autophagy presents a promising therapeutic strategy for overcoming treatment resistance in aggressive cancers.

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Description

This quiz explores the role of growth factor receptors in cancer biology, focusing on their functions and different types, particularly tyrosine kinase receptors. Understanding these receptors is crucial for grasping how signaling molecules regulate cell growth and survival in cancer. Dive into the mechanisms that influence tumor progression and potential therapeutic targets.