BREAST CANCER: A novel therapeutic target for breast cancer targeted molecular subtypes

Running head: BREAST CANCER
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Introduction:
Molecular heterogeneity of Breast cancer has resulted in the disparities in the therapeutic
responses and targeting molecular subtypes of breast cancer. This disparities further intensifying
the necessity of identification and validation of the novel therapeutic target for breast cancer
target (Kiessling and Ashton 2017). Considering the molecular targeting of breast cancer,
POPDC 1 plays a massive role in metastasis behavior of the cancerous cells. POPDC genes are
found throughout the animal kingdom and are a novel class of c-AMP effector with multiple
functions in multiple tissues (Csutak et al. 2016). POPDC protein is a member of membrane-
tethered protein encoded by three members of family POPDC1, 2 and 3 (Pop and Nagy 2016).
Various single cell migration assay suggested that these cells are expressed in cardiac and
skeletal muscles and may act as cell adhesion molecules (Brand 2018). Brand and Schindler
(2016), suggested that suppression of the gene is correlated with the disease progression and
poor clinical outcome in various cancer such as breast cancer, gastric cancer, lungs cancer
hepatocellular sarcoma and colorectal cancer. There is a mountain of literature which suggested
that Popeye domain of POPDC binds to the secondary messenger c-AMP with a high affinity
which predominantly expressed in heart (Di Benedetto , Gerbino and Lefkimmiatis 2018). The
function of this gene, especially POPDC1 is to involve in the cell to cell contact formation and
regulation of epithelial function (Deming et al. 2018). Moreover, it is an essential gene which
shown to be an essential component of tight junctions for proper epithelial cell function
(Rukoyatkina et al. 2018). Loss of POPDC protein expression has been correlated with
increased cancer migration and invasion, drug resistance and poor patient survival (Inoue, Tani
and Tagaya 2016). This paper will illustrate the scope of the review and ration behind it,
molecular structure POPDC, role of POPDC 1 in breast cancer , the interaction between POPDC

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and CAMP, in-depth study of POPDC for drug target ,literature gap, the future direction of
research in following paragraphs.
The scope of the review and the rationale behind choosing the topic:
Various single cell migration assay, cell population migration assay highlighted that
although POPDC proteins are drivers of all kinds of cancer cell migration and proliferation, the
expression pattern is highest in the nonmalignant breast cancer cells and lowest in the malignant
bread cancerous cells (Amunjela 2017). This result further suggested that the loss of POPDC
protein expression correlates with an increase in malignant phenotype of cells that further
increase the health care expenditures and morbidity rate (Mustachio et al. 2016). Therefore,
breast cancer has been chosen for conducting a literature review through primary research. Thus
on a concluding note, this paper intended to conisder and predict molecular targeting of the
Popeye domain of POPDC in breast cancer. Apart from, this paper will give the concise idea of
topic related to POPDC as well as literature gap and the future direction of the research as a
crucial contribution in literature for the readers.
Discussion:
Molecular biology of POPDC:
Tumor growth and metastasis are major challenges in cancer treatment and metastasis
which further increased in the primary cause of more than 90% of deaths of cancer patients with
solid tumor patient (Balaban et al. 2017). Therefore, this incidence further draws the attention of
the researchers for identification of clinically relevant anti-cancer which result in the maximum

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clinical effect with minimal side effects (Peela et al. 2016). Hong et al. (2016), highlighted
that POPDC is an encoded by popdc1, 2 and 3 which is highly expressive in skeletal muscles and
heart muscles and few expression also found in smooth muscle tissue of bladder, the
gastrointestinal tract. The abundance of expression not only limited to these areas but also found
in central and autonomic nervous system, epithelial cells or retina and cornea of eyes. Campbell
et al. (2016), highlighted that these three genes are located in different chromosomal loci and
generally separated by an intragenic sequence and due to overlapping transcription, the
expression of POPDC1 is higher to other two genes (Sharaf et al. 2016). Popeye domain is one
of the unique domains which show the highest level of sequence conservation within POPDC
that further suggested that this protein domain may have further molecular importance. The
affinity of binding with Camp is shared by the POPDC2 and 3 and due to the difference in 20
fold; POPDC1 is preferential binds with the c-AMP. The possible explanation of the affinity also
observed due to the structural similarity between the structural similarities to the cAMP-binding
domain of protein kinase A (PRKAR2B). c-AMP acts as an intracellular massager as well as
further involves in the cell to cell adhesion and interactions (Huang et al. 2016). Upon binding,
POPDC undergoes conformational changes which Furth the cell to cell interaction and regulate
the regulation of the epithelial cell. Therefore, c-AMP regulates the expression of POPDC in
breast cancer.
Role of POPDC 1 in breast cancer:
Breast cancer is the second leading cause of cancer-associated morbidity and mortality
rate worldwide. It classified in luminal A, luminal B, HER2 positive and basal-like according to
the expression of epidermal growth factor receptor 2, estrogen and progesterone expression.
Amunjela and Tucker (2017) conducted a cell proliferation assay, pull-down assay, paired T-