Page 199 - Read Online

Table 1: Involvement of GFRs in cancer progression
Family Receptors Tumor growth Metastasis Angiogenesis induction Cell survival/death Chemoresistance
EGFR/ErbB/ ErbB1 + + Pro-angiogenic Pro-survival signals +
HER ErbB2 + + +
ErbB3 + + ?
ErbB4 + + −
IGFR IGF1R + + Pro-angiogenic + +
IGF2R Suppress growth − − − −
TGF-βR (TβR) TβR I-II Dual role (contextual) + + Dual role +
VEGFR VEGFR1 − ? + + −
VEGFR2 + + + + +
VEGFR3 + + + + +
PDGFR PDGFR (α/β) + + + + +
FGFR FGFR1-4 + + + + +
+/−: Yes/no involvement of growth factor receptor; ?: Not known yet. EGFR: Epidermal growth factor receptor; HER: Human epidermal
growth factor receptor; IGFR: Insulin-like growth factor receptor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-
derived growth factor receptor; FGFR: Fibroblast growth factor receptor; TGF-βR: Transforming growth factor-beta receptor; GFR: Growth
factor receptor

Table 2: GFR expression in cancer
Family Cancer References
EGFR/ Amplifi cation and overexpression of Her1 gene were found in breast (14-91%), bladder, lung, glial (50%) [1]
ErbB/ cancer patients; HER2 gene related to poor prognosis was observed in different malignancies; aggressive
HER metastatic breast (15-30%), gastric (10-30%), ovarian (20-30%), endometrial (1-47%), esophageal (0-83%),
lung (20%), and invasive urothelial bladder (0-80%) carcinomas
Constitutive expression of active truncated EGFR vIII that lacks extracellular domain was found in breast
cancer (20-78%) associated with aggressiveness of tumor
Mutations in HER2 gene in lung, Her3 gene (somatic) in breast, colon, gastric, Her4 gene in melanoma,
colorectal, gastric, lung, and breast cancer were observed in patients
IGFR Amplifi cation of IGF1R gene was reported in small number of breast and melanoma cases [1]
Mutations in IGF2R gene was found in squamous cell carcinomas of the lung
TGF-βR TGF-βRII gene is mutated in colon (58-82%) and pancreatic (4%) cancer, absent in prostate (24%), and [2]
down-regulated in breast and lung cancer
VEGFR High expression of VEGFR1-3 genes was reported in a wide number of malignancies like bladder, brain, [3]
breast, colon, gastric, lung, ovarian, prostate, and head and neck carcinomas
PDGFR Overexpression of PDGFRα gene was found in 20% of glioblastoma [4]
Germline point mutation (gain of function) in PDGFRβ gene was observed in 8 families with infantile
myofi bromatosis
FGFR Amplifi cation of FGFR1-3 genes was observed in different cancer. For example, FGFR1 gene in lung (20%), [5]
breast (10%), ovarian (~5%), bladder (3%); FGFR2 gene in gastric (10%), breast (4% in triple negative);
FGFR3 genein bladder and salivary adenoid cystic cancer
Mutations in FGFR1-4 genes were observed. For example, FGFR1 gene in melanoma (rare), gliblastoma;
FGFR2 gene in endometrial (12%), lung (5%), gastric (rare); FGFR3 gene in bladder (50-60% in
nonmuscle invasive, 10-15% muscle invasive), cervical (5%), prostate (3%), colorectal; FGFR4 gene in
rhabdomyosarcoma (7-8%) cancer
EGFR: Epidermal growth factor receptor; HER: Human epidermal growth factor receptor; IGFR: Insulin-like growth factor receptor;
TGF-βR: Transforming growth factor-beta receptor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived
growth factor receptor; FGFR: Fibroblast growth factor receptor

The relatively simpler IGF2R (also called mannose-6 Transforming growth factor-beta receptor
phosphate receptor, M6P) comprises a single polypeptide
chain, and functions as a “scavenger receptor” for IGF2. The transforming growth factor-beta receptor (TGF-βR)
It suppresses tumor growth, modulates invasiveness, and family comprises three membrane receptors (TβRI,
blocks angiogenesis [Table 1]. Mutations in IGF2R TβRII and TβRIII) which are expressed in diverse types
[12]
[12]
locus have been observed in lung cells and identifi ed of cells and regulate distinct cellular functions by the
as an early event in hepatocellular carcinoma in different signals transduced upon TGF-β ligand binding. TβR
populations. [13] and TβRII are single pass serine/threonine kinases with

192 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦