Lecture 19: Cancer Signalling

Question 1

Signalling pathways __________, _______________, ______________, and _______________ potential are invariably altered in cancer

Answer 1

Signalling pathways controlling cell survival, proliferation, differentiation and migratory potential are invariably altered in cancer

Question 2

Recall the four classes of normal regulatory genes.

Answer 2

Question 3

Recall the molecular/cellular nature of oncogenic factors

Answer 3

Question 4

Recall the concept of oncogene amplification.

Answer 4

Question 5

Recall the generation of oncogenic chimaeric molecules

Answer 5

Due to gene translocations and fusions

Question 6

Recall the generation of genomic chimaeras with aberrant expression

Answer 6

Question 7

Recall examples of pathology immunohistochemical markers for cancer

Answer 7

Question 8

Recall the possible steps in tumour cell proliferation.

Answer 8

Question 9

__________ and ____________ pathways can be activated via Ras.

Answer 9

Question 10

In PI3K pathway, _____ inhibits phosphorylation of Akt by PI3K.

Answer 10

PTEN.

Question 11

Recall the effect of alteration of oncogene-TSG synergy in PI3K pathway.

Answer 11

Question 12

Recall mechanism that results in apoptosis evasion in tumour cells.

Answer 12

Question 13

Exponential growth rate of tumour size is largely assisted by the process of _______________.

Answer 13

Tumour release factor inducing angiogenesis, such as VEGF.

Question 14

Tumour cells avoid senescence by reactivating _____________.

Answer 14

Telomerase, which helps maintain telomere length for each generation.

Note: Senescence refers to the loss of the cell’s ability to divide. While cells that are resistant to senescence have increased replicative capacity, they are still not immortal; instead, they eventually enter into a phase referred to as mitotic crisis and die. This phenomenon has been ascribed to progressive shortening of telomeres at the ends of chromosomes.

Question 15

Recall the process of tumor metastasis.

Answer 15

1. Dissociation of cancer cells from one another is often the result of alterations in intercellular adhesion molecules
2. Degradation of the basement membrane and interstitial connective tissue: secreting proteolytic enzymes themselves or by inducing stromal cells (e.g., fibroblasts and inflammatory cells) to elaborate proteases
3. Changes in attachment of tumor cells to ECM proteins: Loss of adhesion in normal cells leads to induction of apoptosis, while, not surprisingly, tumor cells are resistant to this
4. Locomotion involves propelling tumor cells through the degraded basement membranes and zones of matrix proteolysis

Question 16

Recall the concept of EMT in metastasis.

Answer 16

The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types.

Question 17

Recall the concept of tumour cell heterogeneity.

Answer 17

Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential.

Question 18

Recall cell cycle components and inhibitors that are frequently mutated in cancer.

Answer 18

Question 19

Apoptosis can be initiated through _______ or________ pathways, both of which result in the _________________________.

Answer 19

Apoptosis can be initiated through intrinsic or extrinsic pathways, both of which result in the activation of a proteolytic cascade of caspases that destroys the cell.

Question 20

_________ triggers angiogenesis through the actions of HIF1α on the transcription of the ___________________.

Answer 20

Hypoxia triggers angiogenesis through the actions of HIF1α on the transcription of the proangiogenic factor VEGF.