Cancer cell biology

Question 1

what does colorectal cancer originate from

Answer 1

polyps/small adenomas

Question 2

what is a polyp

Answer 2

abnormal outgrowth of the colonic epithelium

Question 3

what do polyps eventually grow into

Answer 3

carcinomas through a sequence of mutations

Question 4

describe the position of cell types within a colonic crypt

Answer 4

stem cells at the bottom
then proliferating cells
differentiating cells
apoptotic cells

Question 5

what do the stem cells in the crypt develop into

Answer 5

produce other cells that migrate upwards towards the top
enterocytes
goblet cells
enteroendocrine cells
tuft cells

Question 6

function of enterocytes

Answer 6

absorbs water and electrolytes

Question 7

function of goblet cells

Answer 7

secretes mucus

Question 8

function of enteroendocrine cells

Answer 8

secretes hormones

Question 9

function of tuft cells

Answer 9

anti-microbial defence

Question 10

what renews epithelium

Answer 10

the cells migrating upwards and undergo cell death
apoptosis

Question 11

which types of cell division do stem cells undergo

Answer 11

symmetric stem cell division
asymmetric stem cell division
progenitor division
fully differentiated

Question 12

how can colon stem cells be identified

Answer 12

on the basis of the stem cell marker LGR5

Question 13

how are different cells formed from stem cells

Answer 13

transcription factors that are stimulated at different points in the cycle

Question 14

what is Wnt?

Answer 14

wingless/integrated-1
secreted glycoprotein

Question 15

where is Wnt produced?

Answer 15

by the stromal cells at the bottom of the colonic crypts

Question 16

where does Wnt act and what does it bind to?

Answer 16

acts locally, predominantly on the intestinal stem cells
binds to the transmembrane protein receptor called Frizzled (Fz)

Question 17

what does Wnt-Fz activation require

Answer 17

the recruitment of LRP5/6 receptor

Question 18

what does Wnt signalling activation result in?

Answer 18

cytoplasmic activation of Dishevelled (Dsh)

Question 19

what are the 4 proteins involved in the destruction complex?

Answer 19

axin
glycogen synthase kinase 3 GSK3
adenomatous polyposis coli APC
beta-catenin

Question 20

what does Dsh do and what does this result in?

Answer 20

causes axin recruitment to the receptor complex
releases beta-catenin which translocates to the nucleus and functions as a transcription factor
beta-catenin transcribes genes required for cell proliferation

Question 21

what occurs in the absence of Wnt signalling?

Answer 21

destruction complex stays together and self activates
GSK3 phosphorylates beta-catenin
beta-catenin undergoes ubiutination and subsequent proteasomal degradation
results in inhibition of proflieration signal

Question 22

how is APC inactivated?

Answer 22

via forming a smaller truncated protein or mutation

Question 23

what does APC inactivation result in

Answer 23

APC protein that isn’t able to bind to beta catenin
beta-catenin isn’t degraded and functions as transcription factor even in the absence of Wnt signalling

Question 24

what do APC mutations give rise to

Answer 24

beta-catenin levels
cell proliferation continues
cells don’t differentiate
cells don’t undergo apoptosis
gives rise to polyps

Question 25

what is the first step of development of colorectal cancer

Answer 25

genomic instability is a hallmark of cancer leads to DNA damage defects in DNA repair mechanism gives rise to mutations earliest mutations in development of colorectal cancers is APC mutations in APC gives rise to polyps

Question 26

what is FAP

Answer 26

familial adenomatous polyposis autosomal dominant inherited condition patients inherit a mutant copy of APC if left untreated the polyps grow and become malignant APC mutation observed in 35-70% of sporadic colorectal cancers

Question 27

what does a mutation in Ras contribute to and result in?

Answer 27

increase in cell proliferation leads to the development of larger polyps: large adenomas

Question 28

what is the second step of development of colorectal cancer

Answer 28

mutation in APC results in further genetic instability leads to the activation of Ras: oncogenic MAPK signalling

Question 29

what does the additional loss of p53 tumour suppressor result in

Answer 29

failure to arrest cell cycle (absence of CDK inhibitors) failure to induce apoptosis leads to development of colorectal cancer

Question 30

third stage of developing colorectal cancer

Answer 30

breakdown of cell adhesion e.g. loss E-cadherin increased motility/invasiveness

Question 31

what does the inactivation of APC and activation of Ras result in?

Answer 31

sustained and enhanced cell proliferation

Question 32

where can colorectal cancers metastasise to?

Answer 32

liver lungs brain

Question 33

how is the metastasis of colorectal cancer enhanced

Answer 33

by the loss of E-cadherins-proteins that allow epithelial cells to attach to each other increased levels of matrix metalloproteinases MMPS which help breakdown matrix (collagen and proteins)

Question 34

abnormal cell

Answer 34

growing and proliferating uncontrollably

Question 35

neoplasm

Answer 35

mass of abnormal cells known as a tumour

Question 36

benign tumour (dysplasia)

Answer 36

differentiated cells that resemble original cells monomorphic cells, cells that look the same low nuclear to cytoplasmic ratio normochromatic nucleus slowly growing few mitotic cells

Question 37

malignant tumour (dysplasia)

Answer 37

less well differentiated, anaplastic pleomorphic, variation in size and shape high nuclear to cytoplasmic ratio hyperchromatic nucleus fast growing many mitotic cells

Question 38

cancer in situ malignant

Answer 38

entire epithelium replaced by dysplastic cell

Question 39

benign tumour as a cancer

Answer 39

non invasive and localised no metastases

Question 40

malignant tumour as a cancer

Answer 40

invasive metastasise to distant sites

Question 41

benign tumour nomenclature

Answer 41

designed by attaching the suffix -oma

Question 42

nomenclature of a malignant tumour

Answer 42

designed by adding the suffix sarcoma