Epidermal growth factor receptor (EGFR)-RAS signaling pathway in penile squamous cell carcinoma

Hong-Feng Gou1, Xiang Li, Meng Qiu

  • 1Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Plos One
|May 3, 2013
PubMed

Insights

Penile Squamous Cell Carcinoma (SCC) shows high Epidermal Growth Factor Receptor (EGFR) overexpression but rare RASSF1A expression and mutations in KRAS/BRAF. This suggests anti-EGFR therapies may benefit penile SCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Penile Squamous Cell Carcinoma (SCC) is a rare malignancy with a poor prognosis.
  • Limited response to conventional chemotherapy necessitates novel therapeutic strategies.
  • Genetic and epigenetic alterations in the Epidermal Growth Factor Receptor (EGFR)-RAS-RAF pathway in penile SCC remain largely uncharacterized.

Purpose of the Study:

  • To investigate the expression of EGFR and RASSF1A.
  • To determine the mutation status of K-RAS and BRAF in penile SCC.
  • To explore potential therapeutic targets within the EGFR-RAS-RAF signaling pathway.

Main Methods:

  • Immunohistochemistry was used to evaluate EGFR and RASSF1A expression in 150 penile SCC cases.
  • Direct genomic sequencing analyzed KRAS (codons 12, 13) and BRAF (codon 600) mutations.
  • Analysis was performed on DNA from formalin-fixed paraffin-embedded tissues.

Main Results:

  • EGFR expression was detected in all cases, with 92% showing overexpression.
  • RASSF1A expression was found in only 3.42% of cases.
  • KRAS mutations were rare (1/94 samples), and no BRAF V600E mutations were detected (0/83 samples).

Conclusions:

  • The majority of penile SCC cases exhibit EGFR overexpression.
  • RASSF1A expression is infrequent, and KRAS/BRAF mutations are uncommon in penile SCC.
  • Targeted therapy with anti-EGFR agents may represent a promising treatment option for penile SCC.

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...